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char = n;code = 110
char = a;code = 97
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char = i;code = 105
char = c;code = 99
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 = o;code = 111
char = f;code = 102
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = t;code = 116
char = u;code = 117
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = N;code = 78
char = -;code = 45
char = t;code = 116
char = r;code = 114
char = i;code = 105
char = a;code = 97
char = z;code = 122
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = (;code = 40
char = T;code = 84
char = R;code = 82
char = O;code = 79
char = X;code = 88
char = -;code = 45
char = 1;code = 49
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = -;code = 45
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ,;code = 44
char = ;code = 32
char = v;code = 118
char = o;code = 111
char = l;code = 108
char = t;code = 116
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = -;code = 45
char = g;code = 103
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = c;code = 99
char = i;code = 105
char = u;code = 117
char = m;code = 109
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = n;code = 110
char = e;code = 101
char = l;code = 108
char = ;code = 32
char = 2;code = 50
char = ;code = 32
char = b;code = 98
char = l;code = 108
char = o;code = 111
char = c;code = 99
char = k;code = 107
char = e;code = 101
char = r;code = 114
char = .;code = 46
result sql = Analgesic effects of a substituted N-triazole oxindole (TROX-1), a state-dependent, voltage-gated calcium channel 2 blocker.

Analgesic effects of a substituted N-triazole oxindole (TROX-1), a state-dependent, voltage-gated calcium channel 2 blocker.

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char = l;code = 108
char = t;code = 116
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = -;code = 45
char = g;code = 103
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = c;code = 99
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char = ;code = 32
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = n;code = 110
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char = l;code = 108
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char = (;code = 40
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char = a;code = 97
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char = v;code = 118
char = );code = 41
char = );code = 41
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char = 2;code = 50
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char = (;code = 40
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char = p;code = 112
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char = c;code = 99
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char = s;code = 115
char = );code = 41
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = k;code = 107
char = e;code = 101
char = y;code = 121
char = ;code = 32
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char = o;code = 111
char = m;code = 109
char = p;code = 112
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = c;code = 99
char = i;code = 105
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = m;code = 109
char = i;code = 105
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = w;code = 119
char = a;code = 97
char = y;code = 121
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = Z;code = 90
char = i;code = 105
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = -;code = 45
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = p;code = 112
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = d;code = 100
char = e;code = 101
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 = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = C;code = 67
char = a;code = 97
char = (;code = 40
char = v;code = 118
char = );code = 41
char = 2;code = 50
char = .;code = 46
char = 2;code = 50
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = n;code = 110
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = c;code = 99
char = i;code = 105
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = f;code = 102
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = b;code = 98
char = u;code = 117
char = t;code = 116
char = ;code = 32
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char = x;code = 120
char = h;code = 104
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char = b;code = 98
char = i;code = 105
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = n;code = 110
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char = r;code = 114
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char = ;code = 32
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char = h;code = 104
char = e;code = 101
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char = a;code = 97
char = p;code = 112
char = e;code = 101
char = u;code = 117
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char = i;code = 105
char = c;code = 99
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char = n;code = 110
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char = o;code = 111
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char = ;code = 32
char = a;code = 97
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char = ;code = 32
char = m;code = 109
char = u;code = 117
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char = t;code = 116
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char = b;code = 98
char = e;code = 101
char = ;code = 32
char = a;code = 97
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char = m;code = 109
char = i;code = 105
char = n;code = 110
char = i;code = 105
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char = e;code = 101
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char = ;code = 32
char = i;code = 105
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char = r;code = 114
char = a;code = 97
char = t;code = 116
char = h;code = 104
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char = c;code = 99
char = a;code = 97
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char = l;code = 108
char = y;code = 121
char = .;code = 46
char = ;code = 32
char = W;code = 87
char = e;code = 101
char = ;code = 32
char = h;code = 104
char = a;code = 97
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char = e;code = 101
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char = d;code = 100
char = i;code = 105
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char = c;code = 99
char = o;code = 111
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = N;code = 78
char = -;code = 45
char = t;code = 116
char = r;code = 114
char = i;code = 105
char = a;code = 97
char = z;code = 122
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = o;code = 111
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char = i;code = 105
char = n;code = 110
char = d;code = 100
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = (;code = 40
char = 3;code = 51
char = R;code = 82
char = );code = 41
char = -;code = 45
char = 5;code = 53
char = -;code = 45
char = (;code = 40
char = 3;code = 51
char = -;code = 45
char = c;code = 99
char = h;code = 104
char = l;code = 108
char = o;code = 111
char = r;code = 114
char = o;code = 111
char = -;code = 45
char = 4;code = 52
char = -;code = 45
char = f;code = 102
char = l;code = 108
char = u;code = 117
char = o;code = 111
char = r;code = 114
char = o;code = 111
char = p;code = 112
char = h;code = 104
char = e;code = 101
char = n;code = 110
char = y;code = 121
char = l;code = 108
char = );code = 41
char = -;code = 45
char = 3;code = 51
char = -;code = 45
char = m;code = 109
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char = h;code = 104
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char = l;code = 108
char = -;code = 45
char = 3;code = 51
char = -;code = 45
char = (;code = 40
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char = y;code = 121
char = r;code = 114
char = i;code = 105
char = m;code = 109
char = i;code = 105
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = -;code = 45
char = 5;code = 53
char = -;code = 45
char = y;code = 121
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char = m;code = 109
char = e;code = 101
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char = h;code = 104
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char = );code = 41
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char = -;code = 45
char = (;code = 40
char = 1;code = 49
char = H;code = 72
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char = ,;code = 44
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char = l;code = 108
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char = 1;code = 49
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char = h;code = 104
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char = T;code = 84
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char = ,;code = 44
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char = a;code = 97
char = n;code = 110
char = t;code = 116
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char = C;code = 67
char = a;code = 97
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char = 2;code = 50
char = .;code = 46
char = 2;code = 50
char = ;code = 32
char = c;code = 99
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char = i;code = 105
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char = (;code = 40
char = I;code = 73
char = C;code = 67
char = (;code = 40
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char = m;code = 109
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char = c;code = 99
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char = h;code = 104
char = y;code = 121
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char = a;code = 97
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char = z;code = 122
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char = i;code = 105
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char = s;code = 115
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char = 5;code = 53
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char = c;code = 99
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char = n;code = 110
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char = r;code = 114
char = a;code = 97
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char = d;code = 100
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char = r;code = 114
char = s;code = 115
char = a;code = 97
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char = r;code = 114
char = o;code = 111
char = o;code = 111
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char = g;code = 103
char = a;code = 97
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char = g;code = 103
char = l;code = 108
char = i;code = 105
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char = (;code = 40
char = D;code = 68
char = R;code = 82
char = G;code = 71
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char = ;code = 32
char = n;code = 110
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char = u;code = 117
char = r;code = 114
char = o;code = 111
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char = s;code = 115
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char = ;code = 32
char = T;code = 84
char = R;code = 82
char = O;code = 79
char = X;code = 88
char = -;code = 45
char = 1;code = 49
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char = i;code = 105
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char = i;code = 105
char = b;code = 98
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char = t;code = 116
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char = a;code = 97
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char = n;code = 110
char = o;code = 111
char = t;code = 116
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char = G;code = 71
char = V;code = 86
char = I;code = 73
char = A;code = 65
char = -;code = 45
char = s;code = 115
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char = n;code = 110
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
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char = c;code = 99
char = a;code = 97
char = l;code = 108
char = c;code = 99
char = i;code = 105
char = u;code = 117
char = m;code = 109
char = ;code = 32
char = c;code = 99
char = u;code = 117
char = r;code = 114
char = r;code = 114
char = e;code = 101
char = n;code = 110
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char = s;code = 115
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char = C;code = 67
char = a;code = 97
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char = v;code = 118
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char = 2;code = 50
char = .;code = 46
char = 2;code = 50
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char = c;code = 99
char = h;code = 104
char = a;code = 97
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char = n;code = 110
char = e;code = 101
char = l;code = 108
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char = c;code = 99
char = u;code = 117
char = r;code = 114
char = r;code = 114
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char = n;code = 110
char = t;code = 116
char = s;code = 115
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = e;code = 101
char = a;code = 97
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char = e;code = 101
char = r;code = 114
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char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = y;code = 121
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char = u;code = 117
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = r;code = 114
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char = d;code = 100
char = e;code = 101
char = p;code = 112
char = o;code = 111
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = z;code = 122
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = d;code = 100
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = (;code = 40
char = I;code = 73
char = C;code = 67
char = (;code = 40
char = 5;code = 53
char = 0;code = 48
char = );code = 41
char = ;code = 32
char = =;code = 61
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char = 0;code = 48
char = .;code = 46
char = 4;code = 52
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char = m;code = 109
char = i;code = 105
char = c;code = 99
char = r;code = 114
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char = M;code = 77
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char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = n;code = 110
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char = u;code = 117
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = r;code = 114
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char = h;code = 104
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char = p;code = 112
char = e;code = 101
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char = p;code = 112
char = o;code = 111
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = z;code = 122
char = e;code = 101
char = d;code = 100
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char = c;code = 99
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char = n;code = 110
char = d;code = 100
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = (;code = 40
char = I;code = 73
char = C;code = 67
char = (;code = 40
char = 5;code = 53
char = 0;code = 48
char = );code = 41
char = ;code = 32
char = =;code = 61
char = ;code = 32
char = 2;code = 50
char = .;code = 46
char = 6;code = 54
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char = m;code = 109
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char = c;code = 99
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char = o;code = 111
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char = );code = 41
char = ,;code = 44
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char = i;code = 105
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char = d;code = 100
char = i;code = 105
char = c;code = 99
char = a;code = 97
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char = i;code = 105
char = n;code = 110
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char = ;code = 32
char = s;code = 115
char = t;code = 116
char = a;code = 97
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char = e;code = 101
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char = d;code = 100
char = e;code = 101
char = p;code = 112
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = e;code = 101
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char = t;code = 116
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char = C;code = 67
char = a;code = 97
char = (;code = 40
char = v;code = 118
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char = 2;code = 50
char = .;code = 46
char = 2;code = 50
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char = c;code = 99
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char = a;code = 97
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char = e;code = 101
char = l;code = 108
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char = b;code = 98
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char = c;code = 99
char = k;code = 107
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char = a;code = 97
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char = w;code = 119
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char = l;code = 108
char = l;code = 108
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char = a;code = 97
char = s;code = 115
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char = r;code = 114
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char = c;code = 99
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char = i;code = 105
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char = a;code = 97
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char = c;code = 99
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char = a;code = 97
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char = n;code = 110
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = R;code = 82
char = O;code = 79
char = X;code = 88
char = -;code = 45
char = 1;code = 49
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char = f;code = 102
char = u;code = 117
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char = l;code = 108
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char = b;code = 98
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char = o;code = 111
char = c;code = 99
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char = d;code = 100
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char = c;code = 99
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char = i;code = 105
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char = f;code = 102
char = l;code = 108
char = u;code = 117
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char = d;code = 100
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char = a;code = 97
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char = m;code = 109
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char = x;code = 120
char = t;code = 116
char = u;code = 117
char = r;code = 114
char = e;code = 101
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = C;code = 67
char = a;code = 97
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char = v;code = 118
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char = 2;code = 50
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char = c;code = 99
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char = a;code = 97
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char = c;code = 99
char = a;code = 97
char = l;code = 108
char = c;code = 99
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char = u;code = 117
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char = m;code = 109
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char = p;code = 112
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char = r;code = 114
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char = m;code = 109
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char = s;code = 115
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char = n;code = 110
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char = r;code = 114
char = a;code = 97
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char = ;code = 32
char = D;code = 68
char = R;code = 82
char = G;code = 71
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char = n;code = 110
char = e;code = 101
char = u;code = 117
char = r;code = 114
char = o;code = 111
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char = a;code = 97
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char = b;code = 98
char = l;code = 108
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char = c;code = 99
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = a;code = 97
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char = l;code = 108
char = ;code = 32
char = C;code = 67
char = a;code = 97
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char = v;code = 118
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char = 2;code = 50
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char = a;code = 97
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char = i;code = 105
char = l;code = 108
char = y;code = 121
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char = c;code = 99
char = h;code = 104
char = a;code = 97
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char = n;code = 110
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = R;code = 82
char = O;code = 79
char = X;code = 88
char = -;code = 45
char = 1;code = 49
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
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char = e;code = 101
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char = i;code = 105
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char = l;code = 108
char = a;code = 97
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char = m;code = 109
char = a;code = 97
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char = t;code = 116
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char = .;code = 46
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char = I;code = 73
char = n;code = 110
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char = c;code = 99
char = o;code = 111
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char = a;code = 97
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char = a;code = 97
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char = a;code = 97
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char = w;code = 119
char = a;code = 97
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char = b;code = 98
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char = r;code = 114
char = v;code = 118
char = e;code = 101
char = d;code = 100
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char = i;code = 105
char = n;code = 110
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char = C;code = 67
char = a;code = 97
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char = v;code = 118
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char = 2;code = 50
char = .;code = 46
char = 2;code = 50
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char = e;code = 101
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char = e;code = 101
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char = c;code = 99
char = h;code = 104
char = i;code = 105
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = ;code = 32
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char = ;code = 32
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char = h;code = 104
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = p;code = 112
char = e;code = 101
char = u;code = 117
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = o;code = 111
char = w;code = 119
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = i;code = 105
char = t;code = 116
char = a;code = 97
char = b;code = 98
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
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char = r;code = 114
char = e;code = 101
char = a;code = 97
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char = m;code = 109
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char = h;code = 104
char = r;code = 114
char = o;code = 111
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char = i;code = 105
char = c;code = 99
char = ;code = 32
char = p;code = 112
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char = i;code = 105
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result sql = Voltage-gated calcium channel (Ca(v))2.2 (N-type calcium channels) are key components in nociceptive transmission pathways. Ziconotide, a state-independent peptide inhibitor of Ca(v)2.2 channels, is efficacious in treating refractory pain but exhibits a narrow therapeutic window and must be administered intrathecally. We have discovered an N-triazole oxindole, (3R)-5-(3-chloro-4-fluorophenyl)-3-methyl-3-(pyrimidin-5-ylmethyl)-1-(1H-1,2,4-triazol-3-yl)-1,3-dihydro-2H-indol-2-one (TROX-1), as a small-molecule, state-dependent blocker of Ca(v)2 channels, and we investigated the therapeutic advantages of this compound for analgesia. TROX-1 preferentially inhibited potassium-triggered calcium influx through recombinant Ca(v)2.2 channels under depolarized conditions (IC(50) = 0.27 microM) compared with hyperpolarized conditions (IC(50) > 20 microM). In rat dorsal root ganglion (DRG) neurons, TROX-1 inhibited omega-conotoxin GVIA-sensitive calcium currents (Ca(v)2.2 channel currents), with greater potency under depolarized conditions (IC(50) = 0.4 microM) than under hyperpolarized conditions (IC(50) = 2.6 microM), indicating state-dependent Ca(v)2.2 channel block of native as well as recombinant channels. TROX-1 fully blocked calcium influx mediated by a mixture of Ca(v)2 channels in calcium imaging experiments in rat DRG neurons, indicating additional block of all Ca(v)2 family channels. TROX-1 reversed inflammatory-induced hyperalgesia with maximal effects equivalent to nonsteroidal anti-inflammatory drugs, and it reversed nerve injury-induced allodynia to the same extent as pregabalin and duloxetine. In contrast, no significant reversal of hyperalgesia was observed in Ca(v)2.2 gene-deleted mice. Mild impairment of motor function in the Rotarod test and cardiovascular functions were observed at 20- to 40-fold higher plasma concentrations than required for analgesic activities. TROX-1 demonstrates that an orally available state-dependent Ca(v)2 channel blocker may achieve a therapeutic window suitable for the treatment of chronic pain.

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