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result sql = Procognitive 5-HT6 antagonists in the rat forced swimming test: potential therapeutic utility in mood disorders associated with Alzheimer's disease.
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char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = b;code = 98
char = r;code = 114
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = o;code = 111
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = B;code = 66
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = s;code = 115
char = a;code = 97
char = y;code = 121
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = u;code = 117
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = r;code = 114
char = t;code = 116
char = a;code = 97
char = k;code = 107
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = u;code = 117
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = [;code = 91
char = (;code = 40
char = 1;code = 49
char = 2;code = 50
char = 5;code = 53
char = );code = 41
char = I;code = 73
char = ];code = 93
char = S;code = 83
char = B;code = 66
char = -;code = 45
char = 2;code = 50
char = 5;code = 53
char = 8;code = 56
char = 5;code = 53
char = 8;code = 56
char = 5;code = 53
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = b;code = 98
char = r;code = 114
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = 5;code = 53
char = -;code = 45
char = H;code = 72
char = T;code = 84
char = (;code = 40
char = 6;code = 54
char = );code = 41
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = o;code = 111
char = c;code = 99
char = c;code = 99
char = u;code = 117
char = p;code = 112
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = y;code = 121
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = K;code = 75
char = E;code = 69
char = Y;code = 89
char = ;code = 32
char = F;code = 70
char = I;code = 73
char = N;code = 78
char = D;code = 68
char = I;code = 73
char = N;code = 78
char = G;code = 71
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = S;code = 83
char = y;code = 121
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = S;code = 83
char = B;code = 66
char = -;code = 45
char = 3;code = 51
char = 9;code = 57
char = 9;code = 57
char = 8;code = 56
char = 8;code = 56
char = 5;code = 53
char = ;code = 32
char = (;code = 40
char = 3;code = 51
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 1;code = 49
char = 0;code = 48
char = ;code = 32
char = m;code = 109
char = g;code = 103
char = /;code = 47
char = k;code = 107
char = g;code = 103
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = .;code = 46
char = p;code = 112
char = .;code = 46
char = );code = 41
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = S;code = 83
char = B;code = 66
char = -;code = 45
char = 2;code = 50
char = 7;code = 55
char = 1;code = 49
char = 0;code = 48
char = 4;code = 52
char = 6;code = 54
char = ;code = 32
char = (;code = 40
char = 1;code = 49
char = 0;code = 48
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 3;code = 51
char = 0;code = 48
char = ;code = 32
char = m;code = 109
char = g;code = 103
char = /;code = 47
char = k;code = 107
char = g;code = 103
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = .;code = 46
char = p;code = 112
char = .;code = 46
char = );code = 41
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = m;code = 109
char = o;code = 111
char = b;code = 98
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = i;code = 105
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = w;code = 119
char = i;code = 105
char = m;code = 109
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = m;code = 109
char = i;code = 105
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = f;code = 102
char = i;code = 105
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = 5;code = 53
char = -;code = 45
char = H;code = 72
char = T;code = 84
char = (;code = 40
char = 6;code = 54
char = );code = 41
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = o;code = 111
char = c;code = 99
char = c;code = 99
char = u;code = 117
char = p;code = 112
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = y;code = 121
char = ;code = 32
char = (;code = 40
char = 6;code = 54
char = 2;code = 50
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 9;code = 57
char = 6;code = 54
char = %;code = 37
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = 3;code = 51
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 1;code = 49
char = 0;code = 48
char = ;code = 32
char = m;code = 109
char = g;code = 103
char = /;code = 47
char = k;code = 107
char = g;code = 103
char = ;code = 32
char = S;code = 83
char = B;code = 66
char = -;code = 45
char = 3;code = 51
char = 9;code = 57
char = 9;code = 57
char = 8;code = 56
char = 8;code = 56
char = 5;code = 53
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = ;;code = 59
char = ;code = 32
char = 5;code = 53
char = 6;code = 54
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 8;code = 56
char = 4;code = 52
char = %;code = 37
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = 1;code = 49
char = 0;code = 48
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 3;code = 51
char = 0;code = 48
char = ;code = 32
char = m;code = 109
char = g;code = 103
char = /;code = 47
char = k;code = 107
char = g;code = 103
char = ;code = 32
char = S;code = 83
char = B;code = 66
char = -;code = 45
char = 2;code = 50
char = 7;code = 55
char = 1;code = 49
char = 0;code = 48
char = 4;code = 52
char = 6;code = 54
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = );code = 41
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = ,;code = 44
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = p;code = 112
char = e;code = 101
char = z;code = 122
char = i;code = 105
char = l;code = 108
char = ;code = 32
char = (;code = 40
char = 0;code = 48
char = .;code = 46
char = 5;code = 53
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 1;code = 49
char = ;code = 32
char = m;code = 109
char = g;code = 103
char = /;code = 47
char = k;code = 107
char = g;code = 103
char = ;code = 32
char = i;code = 105
char = .;code = 46
char = p;code = 112
char = .;code = 46
char = );code = 41
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = y;code = 121
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = e;code = 101
char = l;code = 108
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = S;code = 83
char = I;code = 73
char = G;code = 71
char = N;code = 78
char = I;code = 73
char = F;code = 70
char = I;code = 73
char = C;code = 67
char = A;code = 65
char = N;code = 78
char = C;code = 67
char = E;code = 69
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = a;code = 97
char = t;code = 116
char = a;code = 97
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char = s;code = 115
char = u;code = 117
char = g;code = 103
char = g;code = 103
char = e;code = 101
char = s;code = 115
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char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = 5;code = 53
char = -;code = 45
char = H;code = 72
char = T;code = 84
char = (;code = 40
char = 6;code = 54
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char = ;code = 32
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char = t;code = 116
char = a;code = 97
char = g;code = 103
char = o;code = 111
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char = i;code = 105
char = s;code = 115
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char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = a;code = 97
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char = e;code = 101
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char = c;code = 99
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char = i;code = 105
char = n;code = 110
char = g;code = 103
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char = t;code = 116
char = o;code = 111
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char = h;code = 104
char = o;code = 111
char = s;code = 115
char = e;code = 101
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char = o;code = 111
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char = c;code = 99
char = u;code = 117
char = p;code = 112
char = y;code = 121
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char = c;code = 99
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = 5;code = 53
char = -;code = 45
char = H;code = 72
char = T;code = 84
char = (;code = 40
char = 6;code = 54
char = );code = 41
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = u;code = 117
char = l;code = 108
char = d;code = 100
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = v;code = 118
char = e;code = 101
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char = a;code = 97
char = n;code = 110
char = ;code = 32
char = a;code = 97
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char = t;code = 116
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = h;code = 104
char = u;code = 117
char = m;code = 109
char = a;code = 97
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char = s;code = 115
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = y;code = 121
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = 5;code = 53
char = -;code = 45
char = H;code = 72
char = T;code = 84
char = (;code = 40
char = 6;code = 54
char = );code = 41
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = g;code = 103
char = o;code = 111
char = n;code = 110
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = A;code = 65
char = C;code = 67
char = h;code = 104
char = E;code = 69
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = o;code = 111
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char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = m;code = 109
char = o;code = 111
char = o;code = 111
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = o;code = 111
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char = t;code = 116
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = i;code = 105
char = n;code = 110
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result sql = AIMS : 5-HT(6) receptor subtype is predominantly expressed in the brain, and preclinical evidence suggests its potential role in the cognitive function. Brain microdialysis studies demonstrated that 5-HT(6) antagonists enhance not only cholinergic but also monoaminergic neurotransmission, a property that may differentiate from acetylcholine esterase (AChE) inhibitors such as donepezil. In this study we compared the antidepressant-like effects of 5-HT(6) antagonists with donepezil to determine whether their different effects on monoamines are behaviorally relevant.
MAIN METHODS : Selective 5-HT(6) antagonists (SB-399885 and SB-271046) and donepezil were evaluated in the rat forced swimming test since this is known to identify drugs such as antidepressants which can increase brain monoamine levels. Binding assay was undertaken by using [(125)I]SB-258585 to measure brain 5-HT(6) receptor occupancy.
KEY FINDINGS : Systemic administration of SB-399885 (3 and 10 mg/kg, i.p.) and SB-271046 (10 and 30 mg/kg, i.p.) produced a significant reduction of immobility time in the rat forced swimming test with a similar profile in terms of 5-HT(6) receptor occupancy (62 and 96% for 3 and 10 mg/kg SB-399885 respectively; 56 and 84% for 10 and 30 mg/kg SB-271046 respectively). In contrast, donepezil (0.5 and 1 mg/kg i.p.) did not show any effects in this model.
SIGNIFICANCE : These data suggest that 5-HT(6) antagonists, at doses corresponding to those occupy central 5-HT(6) receptors, could have an antidepressive effect in humans. This may differentiate 5-HT(6) antagonists from AChE inhibitors with respect to the mood control in the symptomatic treatment of Alzheimer's disease.
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result sql = Procognitive 5-HT6 antagonists in the rat forced swimming test: potential therapeutic utility in mood disorders associated with Alzheimer's disease.
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char = l;code = 108
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = u;code = 117
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = w;code = 119
char = i;code = 105
char = m;code = 109
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = k;code = 107
char = n;code = 110
char = o;code = 111
char = w;code = 119
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = f;code = 102
char = y;code = 121
char = ;code = 32
char = d;code = 100
char = r;code = 114
char = u;code = 117
char = g;code = 103
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = b;code = 98
char = r;code = 114
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = o;code = 111
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = B;code = 66
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = s;code = 115
char = a;code = 97
char = y;code = 121
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = u;code = 117
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = r;code = 114
char = t;code = 116
char = a;code = 97
char = k;code = 107
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = u;code = 117
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = [;code = 91
char = (;code = 40
char = 1;code = 49
char = 2;code = 50
char = 5;code = 53
char = );code = 41
char = I;code = 73
char = ];code = 93
char = S;code = 83
char = B;code = 66
char = -;code = 45
char = 2;code = 50
char = 5;code = 53
char = 8;code = 56
char = 5;code = 53
char = 8;code = 56
char = 5;code = 53
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = b;code = 98
char = r;code = 114
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = 5;code = 53
char = -;code = 45
char = H;code = 72
char = T;code = 84
char = (;code = 40
char = 6;code = 54
char = );code = 41
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = o;code = 111
char = c;code = 99
char = c;code = 99
char = u;code = 117
char = p;code = 112
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = y;code = 121
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = K;code = 75
char = E;code = 69
char = Y;code = 89
char = ;code = 32
char = F;code = 70
char = I;code = 73
char = N;code = 78
char = D;code = 68
char = I;code = 73
char = N;code = 78
char = G;code = 71
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = S;code = 83
char = y;code = 121
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = S;code = 83
char = B;code = 66
char = -;code = 45
char = 3;code = 51
char = 9;code = 57
char = 9;code = 57
char = 8;code = 56
char = 8;code = 56
char = 5;code = 53
char = ;code = 32
char = (;code = 40
char = 3;code = 51
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 1;code = 49
char = 0;code = 48
char = ;code = 32
char = m;code = 109
char = g;code = 103
char = /;code = 47
char = k;code = 107
char = g;code = 103
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = .;code = 46
char = p;code = 112
char = .;code = 46
char = );code = 41
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = S;code = 83
char = B;code = 66
char = -;code = 45
char = 2;code = 50
char = 7;code = 55
char = 1;code = 49
char = 0;code = 48
char = 4;code = 52
char = 6;code = 54
char = ;code = 32
char = (;code = 40
char = 1;code = 49
char = 0;code = 48
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 3;code = 51
char = 0;code = 48
char = ;code = 32
char = m;code = 109
char = g;code = 103
char = /;code = 47
char = k;code = 107
char = g;code = 103
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = .;code = 46
char = p;code = 112
char = .;code = 46
char = );code = 41
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = m;code = 109
char = o;code = 111
char = b;code = 98
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = i;code = 105
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = w;code = 119
char = i;code = 105
char = m;code = 109
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = m;code = 109
char = i;code = 105
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = f;code = 102
char = i;code = 105
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = 5;code = 53
char = -;code = 45
char = H;code = 72
char = T;code = 84
char = (;code = 40
char = 6;code = 54
char = );code = 41
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = o;code = 111
char = c;code = 99
char = c;code = 99
char = u;code = 117
char = p;code = 112
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = y;code = 121
char = ;code = 32
char = (;code = 40
char = 6;code = 54
char = 2;code = 50
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 9;code = 57
char = 6;code = 54
char = %;code = 37
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = 3;code = 51
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 1;code = 49
char = 0;code = 48
char = ;code = 32
char = m;code = 109
char = g;code = 103
char = /;code = 47
char = k;code = 107
char = g;code = 103
char = ;code = 32
char = S;code = 83
char = B;code = 66
char = -;code = 45
char = 3;code = 51
char = 9;code = 57
char = 9;code = 57
char = 8;code = 56
char = 8;code = 56
char = 5;code = 53
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = ;;code = 59
char = ;code = 32
char = 5;code = 53
char = 6;code = 54
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 8;code = 56
char = 4;code = 52
char = %;code = 37
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = 1;code = 49
char = 0;code = 48
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 3;code = 51
char = 0;code = 48
char = ;code = 32
char = m;code = 109
char = g;code = 103
char = /;code = 47
char = k;code = 107
char = g;code = 103
char = ;code = 32
char = S;code = 83
char = B;code = 66
char = -;code = 45
char = 2;code = 50
char = 7;code = 55
char = 1;code = 49
char = 0;code = 48
char = 4;code = 52
char = 6;code = 54
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = );code = 41
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = ,;code = 44
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = p;code = 112
char = e;code = 101
char = z;code = 122
char = i;code = 105
char = l;code = 108
char = ;code = 32
char = (;code = 40
char = 0;code = 48
char = .;code = 46
char = 5;code = 53
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 1;code = 49
char = ;code = 32
char = m;code = 109
char = g;code = 103
char = /;code = 47
char = k;code = 107
char = g;code = 103
char = ;code = 32
char = i;code = 105
char = .;code = 46
char = p;code = 112
char = .;code = 46
char = );code = 41
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = y;code = 121
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = e;code = 101
char = l;code = 108
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = S;code = 83
char = I;code = 73
char = G;code = 71
char = N;code = 78
char = I;code = 73
char = F;code = 70
char = I;code = 73
char = C;code = 67
char = A;code = 65
char = N;code = 78
char = C;code = 67
char = E;code = 69
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = a;code = 97
char = t;code = 116
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = g;code = 103
char = g;code = 103
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = 5;code = 53
char = -;code = 45
char = H;code = 72
char = T;code = 84
char = (;code = 40
char = 6;code = 54
char = );code = 41
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = g;code = 103
char = o;code = 111
char = n;code = 110
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = r;code = 114
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = o;code = 111
char = n;code = 110
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = c;code = 99
char = c;code = 99
char = u;code = 117
char = p;code = 112
char = y;code = 121
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = 5;code = 53
char = -;code = 45
char = H;code = 72
char = T;code = 84
char = (;code = 40
char = 6;code = 54
char = );code = 41
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = u;code = 117
char = l;code = 108
char = d;code = 100
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = h;code = 104
char = u;code = 117
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = a;code = 97
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result sql = AIMS : 5-HT(6) receptor subtype is predominantly expressed in the brain, and preclinical evidence suggests its potential role in the cognitive function. Brain microdialysis studies demonstrated that 5-HT(6) antagonists enhance not only cholinergic but also monoaminergic neurotransmission, a property that may differentiate from acetylcholine esterase (AChE) inhibitors such as donepezil. In this study we compared the antidepressant-like effects of 5-HT(6) antagonists with donepezil to determine whether their different effects on monoamines are behaviorally relevant.
MAIN METHODS : Selective 5-HT(6) antagonists (SB-399885 and SB-271046) and donepezil were evaluated in the rat forced swimming test since this is known to identify drugs such as antidepressants which can increase brain monoamine levels. Binding assay was undertaken by using [(125)I]SB-258585 to measure brain 5-HT(6) receptor occupancy.
KEY FINDINGS : Systemic administration of SB-399885 (3 and 10 mg/kg, i.p.) and SB-271046 (10 and 30 mg/kg, i.p.) produced a significant reduction of immobility time in the rat forced swimming test with a similar profile in terms of 5-HT(6) receptor occupancy (62 and 96% for 3 and 10 mg/kg SB-399885 respectively; 56 and 84% for 10 and 30 mg/kg SB-271046 respectively). In contrast, donepezil (0.5 and 1 mg/kg i.p.) did not show any effects in this model.
SIGNIFICANCE : These data suggest that 5-HT(6) antagonists, at doses corresponding to those occupy central 5-HT(6) receptors, could have an antidepressive effect in humans. This may differentiate 5-HT(6) antagonists from AChE inhibitors with respect to the mood control in the symptomatic treatment of Alzheimer's disease.
Publication: Life Sci. 2009 Apr 10 ;84(15-16)::558-62. :doi: 10.1016/j.lfs.2009.01.019.
Publication Date: 2009 Apr 10
Study Author(s): Hirano, Kazufumi;Piers, Thomas M;Searle, Kirsten L;Miller, Neil D;Rutter, A Richard;Chapman, Paul F;
Institution: Cognition & Neurodegeneration Centre, Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, #03-01/02, The Helios, 11 Biopolis Way, Singapore. [email protected]
Shortcut link to this study:
Publication Date: 2009 Apr 10
Study Author(s): Hirano, Kazufumi;Piers, Thomas M;Searle, Kirsten L;Miller, Neil D;Rutter, A Richard;Chapman, Paul F;
Institution: Cognition & Neurodegeneration Centre, Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, #03-01/02, The Helios, 11 Biopolis Way, Singapore. [email protected]
Shortcut link to this study:
AIMS : 5-HT(6) receptor subtype is predominantly expressed in the brain, and preclinical evidence suggests its potential role in the cognitive function. Brain microdialysis studies demonstrated that 5-HT(6) antagonists enhance not only cholinergic but also monoaminergic neurotransmission, a property that may differentiate from acetylcholine esterase (AChE) inhibitors such as donepezil. In this study we compared the antidepressant-like effects of 5-HT(6) antagonists with donepezil to determine whether their different effects on monoamines are behaviorally relevant.
MAIN METHODS : Selective 5-HT(6) antagonists (SB-399885 and SB-271046) and donepezil were evaluated in the rat forced swimming test since this is known to identify drugs such as antidepressants which can increase brain monoamine levels. Binding assay was undertaken by using [(125)I]SB-258585 to measure brain 5-HT(6) receptor occupancy.
KEY FINDINGS : Systemic administration of SB-399885 (3 and 10 mg/kg, i.p.) and SB-271046 (10 and 30 mg/kg, i.p.) produced a significant reduction of immobility time in the rat forced swimming test with a similar profile in terms of 5-HT(6) receptor occupancy (62 and 96% for 3 and 10 mg/kg SB-399885 respectively; 56 and 84% for 10 and 30 mg/kg SB-271046 respectively). In contrast, donepezil (0.5 and 1 mg/kg i.p.) did not show any effects in this model.
SIGNIFICANCE : These data suggest that 5-HT(6) antagonists, at doses corresponding to those occupy central 5-HT(6) receptors, could have an antidepressive effect in humans. This may differentiate 5-HT(6) antagonists from AChE inhibitors with respect to the mood control in the symptomatic treatment of Alzheimer's disease.
MAIN METHODS : Selective 5-HT(6) antagonists (SB-399885 and SB-271046) and donepezil were evaluated in the rat forced swimming test since this is known to identify drugs such as antidepressants which can increase brain monoamine levels. Binding assay was undertaken by using [(125)I]SB-258585 to measure brain 5-HT(6) receptor occupancy.
KEY FINDINGS : Systemic administration of SB-399885 (3 and 10 mg/kg, i.p.) and SB-271046 (10 and 30 mg/kg, i.p.) produced a significant reduction of immobility time in the rat forced swimming test with a similar profile in terms of 5-HT(6) receptor occupancy (62 and 96% for 3 and 10 mg/kg SB-399885 respectively; 56 and 84% for 10 and 30 mg/kg SB-271046 respectively). In contrast, donepezil (0.5 and 1 mg/kg i.p.) did not show any effects in this model.
SIGNIFICANCE : These data suggest that 5-HT(6) antagonists, at doses corresponding to those occupy central 5-HT(6) receptors, could have an antidepressive effect in humans. This may differentiate 5-HT(6) antagonists from AChE inhibitors with respect to the mood control in the symptomatic treatment of Alzheimer's disease.
PMID: 19302808
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