char = T;code = 84 char = r;code = 114 char = i;code = 105 char = c;code = 99 char = y;code = 121 char = c;code = 99 char = l;code = 108 char = i;code = 105 char = c;code = 99 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 = 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 = ;code = 32 char = h;code = 104 char = o;code = 111 char = m;code = 109 char = o;code = 111 char = m;code = 109 char = e;code = 101 char = r;code = 114 char = i;code = 105 char = c;code = 99 char = ;code = 32 char = C;code = 67 char = y;code = 121 char = s;code = 115 char = -;code = 45 char = l;code = 108 char = o;code = 111 char = o;code = 111 char = p;code = 112 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 = 32 char = b;code = 98 char = y;code = 121 char = ;code = 32 char = a;code = 97 char = c;code = 99 char = t;code = 116 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = a;code = 97 char = t;code = 116 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 = ;code = 32 char = c;code = 99 char = o;code = 111 char = n;code = 110 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = m;code = 109 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = s;code = 115 char = t;code = 116 char = a;code = 97 char = t;code = 116 char = e;code = 101 char = s;code = 115 char = .;code = 46 result sql = Tricyclic antidepressants inhibit homomeric Cys-loop receptors by acting at different conformational states.
Tricyclic antidepressants inhibit homomeric Cys-loop receptors by acting at different conformational states.char = T;code = 84 char = r;code = 114 char = i;code = 105 char = c;code = 99 char = y;code = 121 char = c;code = 99 char = l;code = 108 char = i;code = 105 char = c;code = 99 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 = n;code = 110 char = o;code = 111 char = t;code = 116 char = ;code = 32 char = o;code = 111 char = n;code = 110 char = l;code = 108 char = y;code = 121 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 = ;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 = r;code = 114 char = e;code = 101 char = u;code = 117 char = p;code = 112 char = t;code = 116 char = a;code = 97 char = k;code = 107 char = e;code = 101 char = ;code = 32 char = b;code = 98 char = u;code = 117 char = t;code = 116 char = ;code = 32 char = a;code = 97 char = l;code = 108 char = s;code = 115 char = o;code = 111 char = ;code = 32 char = m;code = 109 char = o;code = 111 char = d;code = 100 char = u;code = 117 char = l;code = 108 char = a;code = 97 char = t;code = 116 char = e;code = 101 char = ;code = 32 char = C;code = 67 char = y;code = 121 char = s;code = 115 char = -;code = 45 char = l;code = 108 char = o;code = 111 char = o;code = 111 char = p;code = 112 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 = 46 char = ;code = 32 char = H;code = 72 char = o;code = 111 char = w;code = 119 char = e;code = 101 char = v;code = 118 char = e;code = 101 char = r;code = 114 char = ,;code = 44 char = ;code = 32 char = i;code = 105 char = t;code = 116 char = ;code = 32 char = i;code = 105 char = s;code = 115 char = ;code = 32 char = n;code = 110 char = o;code = 111 char = t;code = 116 char = ;code = 32 char = u;code = 117 char = n;code = 110 char = d;code = 100 char = e;code = 101 char = r;code = 114 char = s;code = 115 char = t;code = 116 char = o;code = 111 char = o;code = 111 char = d;code = 100 char = ;code = 32 char = h;code = 104 char = o;code = 111 char = w;code = 119 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 = u;code = 117 char = l;code = 108 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = i;code = 105 char = s;code = 115 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = v;code = 118 char = o;code = 111 char = l;code = 108 char = v;code = 118 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 = i;code = 105 char = r;code = 114 char = ;code = 32 char = t;code = 116 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 = 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 = 46 char = ;code = 32 char = W;code = 87 char = e;code = 101 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = a;code = 97 char = l;code = 108 char = y;code = 121 char = z;code = 122 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = m;code = 109 char = e;code = 101 char = c;code = 99 char = h;code = 104 char = a;code = 97 char = n;code = 110 char = i;code = 105 char = s;code = 115 char = m;code = 109 char = s;code = 115 char = ;code = 32 char = o;code = 111 char = f;code = 102 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 = 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 = h;code = 104 char = o;code = 111 char = m;code = 109 char = o;code = 111 char = m;code = 109 char = e;code = 101 char = r;code = 114 char = i;code = 105 char = c;code = 99 char = ;code = 32 char = 5;code = 53 char = -;code = 45 char = H;code = 72 char = T;code = 84 char = (;code = 40 char = 3;code = 51 char = A;code = 65 char = );code = 41 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = a;code = 97 char = l;code = 108 char = p;code = 112 char = h;code = 104 char = a;code = 97 char = 7;code = 55 char = -;code = 45 char = 5;code = 53 char = H;code = 72 char = T;code = 84 char = (;code = 40 char = 3;code = 51 char = A;code = 65 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 = 32 char = b;code = 98 char = y;code = 121 char = ;code = 32 char = t;code = 116 char = r;code = 114 char = i;code = 105 char = c;code = 99 char = y;code = 121 char = c;code = 99 char = l;code = 108 char = i;code = 105 char = c;code = 99 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 = a;code = 97 char = t;code = 116 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = s;code = 115 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = l;code = 108 char = e;code = 101 char = -;code = 45 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 = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = m;code = 109 char = a;code = 97 char = c;code = 99 char = r;code = 114 char = o;code = 111 char = s;code = 115 char = c;code = 99 char = o;code = 111 char = p;code = 112 char = i;code = 105 char = c;code = 99 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 char = t;code = 116 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 = 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 = r;code = 114 char = u;code = 117 char = g;code = 103 char = s;code = 115 char = ;code = 32 char = r;code = 114 char = e;code = 101 char = d;code = 100 char = u;code = 117 char = c;code = 99 char = e;code = 101 char = ;code = 32 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 = -;code = 45 char = e;code = 101 char = v;code = 118 char = o;code = 111 char = k;code = 107 char = e;code = 101 char = d;code = 100 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 char = t;code = 116 char = s;code = 115 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = a;code = 97 char = ;code = 32 char = n;code = 110 char = o;code = 111 char = n;code = 110 char = c;code = 99 char = o;code = 111 char = m;code = 109 char = p;code = 112 char = e;code = 101 char = t;code = 116 char = i;code = 105 char = t;code = 116 char = i;code = 105 char = v;code = 118 char = e;code = 101 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = n;code = 110 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 = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 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 = 32 char = m;code = 109 char = a;code = 97 char = n;code = 110 char = n;code = 110 char = e;code = 101 char = r;code = 114 char = .;code = 46 char = ;code = 32 char = W;code = 87 char = h;code = 104 char = e;code = 101 char = n;code = 110 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = y;code = 121 char = ;code = 32 char = a;code = 97 char = c;code = 99 char = t;code = 116 char = ;code = 32 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = o;code = 111 char = p;code = 112 char = e;code = 101 char = n;code = 110 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 = 44 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 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 = i;code = 105 char = s;code = 115 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 = f;code = 102 char = o;code = 111 char = r;code = 114 char = ;code = 32 char = b;code = 98 char = o;code = 111 char = t;code = 116 char = h;code = 104 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 = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = i;code = 105 char = t;code = 116 char = ;code = 32 char = i;code = 105 char = s;code = 115 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 = 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 = t;code = 116 char = h;code = 104 char = u;code = 117 char = s;code = 115 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 = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = ;code = 32 char = o;code = 111 char = p;code = 112 char = e;code = 101 char = n;code = 110 char = -;code = 45 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 = b;code = 98 char = l;code = 108 char = o;code = 111 char = c;code = 99 char = k;code = 107 char = ;code = 32 char = p;code = 112 char = r;code = 114 char = o;code = 111 char = c;code = 99 char = e;code = 101 char = s;code = 115 char = s;code = 115 char = ;code = 32 char = i;code = 105 char = n;code = 110 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 = t;code = 116 char = h;code = 104 char = e;code = 101 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 = d;code = 100 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 = c;code = 99 char = a;code = 97 char = n;code = 110 char = ;code = 32 char = e;code = 101 char = i;code = 105 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = r;code = 114 char = ;code = 32 char = c;code = 99 char = l;code = 108 char = o;code = 111 char = s;code = 115 char = e;code = 101 char = ;code = 32 char = o;code = 111 char = r;code = 114 char = ;code = 32 char = r;code = 114 char = e;code = 101 char = m;code = 109 char = a;code = 97 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = s;code = 115 char = t;code = 116 char = a;code = 97 char = b;code = 98 char = i;code = 105 char = l;code = 108 char = i;code = 105 char = z;code = 122 char = e;code = 101 char = d;code = 100 char = .;code = 46 char = ;code = 32 char = B;code = 66 char = y;code = 121 char = ;code = 32 char = a;code = 97 char = c;code = 99 char = t;code = 116 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = o;code = 111 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 = e;code = 101 char = s;code = 115 char = t;code = 116 char = i;code = 105 char = n;code = 110 char = g;code = 103 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 = 44 char = ;code = 32 char = t;code = 116 char = r;code = 114 char = i;code = 105 char = c;code = 99 char = y;code = 121 char = c;code = 99 char = l;code = 108 char = i;code = 105 char = c;code = 99 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 = r;code = 114 char = e;code = 101 char = d;code = 100 char = u;code = 117 char = c;code = 99 char = e;code = 101 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = p;code = 112 char = e;code = 101 char = a;code = 97 char = k;code = 107 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 char = t;code = 116 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = a;code = 97 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 = 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 = m;code = 109 char = a;code = 97 char = n;code = 110 char = n;code = 110 char = e;code = 101 char = r;code = 114 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 = a;code = 97 char = ;code = 32 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 char = ;code = 32 char = 6;code = 54 char = -;code = 45 char = f;code = 102 char = o;code = 111 char = l;code = 108 char = d;code = 100 char = ;code = 32 char = h;code = 104 char = i;code = 105 char = g;code = 103 char = h;code = 104 char = e;code = 101 char = r;code = 114 char = ;code = 32 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = ;code = 32 char = 5;code = 53 char = -;code = 45 char = H;code = 72 char = T;code = 84 char = (;code = 40 char = 3;code = 51 char = A;code = 65 char = );code = 41 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = a;code = 97 char = n;code = 110 char = ;code = 32 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = ;code = 32 char = a;code = 97 char = l;code = 108 char = p;code = 112 char = h;code = 104 char = a;code = 97 char = 7;code = 55 char = -;code = 45 char = 5;code = 53 char = H;code = 72 char = T;code = 84 char = (;code = 40 char = 3;code = 51 char = A;code = 65 char = );code = 41 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 = 58 char = ;code = 32 char = 6;code = 54 char = ;code = 32 char = m;code = 109 char = i;code = 105 char = c;code = 99 char = r;code = 114 char = o;code = 111 char = M;code = 77 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 = i;code = 105 char = c;code = 99 char = r;code = 114 char = o;code = 111 char = M;code = 77 char = ;code = 32 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = ;code = 32 char = a;code = 97 char = l;code = 108 char = p;code = 112 char = h;code = 104 char = a;code = 97 char = 7;code = 55 char = -;code = 45 char = 5;code = 53 char = H;code = 72 char = T;code = 84 char = (;code = 40 char = 3;code = 51 char = A;code = 65 char = );code = 41 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = 5;code = 53 char = -;code = 45 char = H;code = 72 char = T;code = 84 char = (;code = 40 char = 3;code = 51 char = A;code = 65 char = );code = 41 char = ,;code = 44 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 = T;code = 84 char = h;code = 104 char = u;code = 117 char = s;code = 115 char = ,;code = 44 char = ;code = 32 char = t;code = 116 char = r;code = 114 char = i;code = 105 char = c;code = 99 char = y;code = 121 char = c;code = 99 char = l;code = 108 char = i;code = 105 char = c;code = 99 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 = m;code = 109 char = a;code = 97 char = y;code = 121 char = ;code = 32 char = a;code = 97 char = c;code = 99 char = t;code = 116 char = ;code = 32 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = c;code = 99 char = l;code = 108 char = o;code = 111 char = s;code = 115 char = e;code = 101 char = d;code = 100 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 = 32 char = a;code = 97 char = t;code = 116 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = u;code = 117 char = n;code = 110 char = s;code = 115 char = h;code = 104 char = a;code = 97 char = r;code = 114 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = e;code = 101 char = x;code = 120 char = t;code = 116 char = r;code = 114 char = a;code = 97 char = c;code = 99 char = e;code = 101 char = l;code = 108 char = l;code = 108 char = u;code = 117 char = l;code = 108 char = a;code = 97 char = r;code = 114 char = ;code = 32 char = d;code = 100 char = o;code = 111 char = m;code = 109 char = a;code = 97 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = f;code = 102 char = r;code = 114 char = o;code = 111 char = m;code = 109 char = ;code = 32 char = w;code = 119 char = h;code = 104 char = e;code = 101 char = r;code = 114 char = e;code = 101 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = y;code = 121 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 = ;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 = o;code = 111 char = p;code = 112 char = e;code = 101 char = n;code = 110 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = .;code = 46 char = ;code = 32 char = S;code = 83 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = l;code = 108 char = e;code = 101 char = ;code = 32 char = a;code = 97 char = l;code = 108 char = p;code = 112 char = h;code = 104 char = a;code = 97 char = 7;code = 55 char = -;code = 45 char = 5;code = 53 char = H;code = 72 char = T;code = 84 char = (;code = 40 char = 3;code = 51 char = A;code = 65 char = );code = 41 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 = 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 = c;code = 99 char = o;code = 111 char = n;code = 110 char = t;code = 116 char = i;code = 105 char = n;code = 110 char = u;code = 117 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = p;code = 112 char = r;code = 114 char = e;code = 101 char = s;code = 115 char = e;code = 101 char = n;code = 110 char = c;code = 99 char = e;code = 101 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = t;code = 116 char = r;code = 114 char = i;code = 105 char = c;code = 99 char = y;code = 121 char = c;code = 99 char = l;code = 108 char = i;code = 105 char = c;code = 99 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 = s;code = 115 char = h;code = 104 char = o;code = 111 char = w;code = 119 char = :;code = 58 char = ;code = 32 char = i;code = 105 char = );code = 41 char = ;code = 32 char = r;code = 114 char = e;code = 101 char = d;code = 100 char = u;code = 117 char = c;code = 99 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = o;code = 111 char = p;code = 112 char = e;code = 101 char = n;code = 110 char = ;code = 32 char = d;code = 100 char = u;code = 117 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 = s;code = 115 char = ,;code = 44 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = m;code = 109 char = p;code = 112 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = b;code = 98 char = l;code = 108 char = e;code = 101 char = ;code = 32 char = w;code = 119 char = i;code = 105 char = t;code = 116 char = h;code = 104 char = ;code = 32 char = o;code = 111 char = p;code = 112 char = e;code = 101 char = n;code = 110 char = -;code = 45 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 = b;code = 98 char = l;code = 108 char = o;code = 111 char = c;code = 99 char = k;code = 107 char = ;;code = 59 char = ;code = 32 char = i;code = 105 char = i;code = 105 char = );code = 41 char = ;code = 32 char = r;code = 114 char = e;code = 101 char = d;code = 100 char = u;code = 117 char = c;code = 99 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = b;code = 98 char = u;code = 117 char = r;code = 114 char = s;code = 115 char = t;code = 116 char = ;code = 32 char = d;code = 100 char = u;code = 117 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 = s;code = 115 char = ,;code = 44 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = m;code = 109 char = p;code = 112 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = b;code = 98 char = l;code = 108 char = e;code = 101 char = ;code = 32 char = w;code = 119 char = i;code = 105 char = t;code = 116 char = h;code = 104 char = ;code = 32 char = c;code = 99 char = l;code = 108 char = o;code = 111 char = s;code = 115 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = o;code = 111 char = f;code = 102 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 = d;code = 100 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 = 59 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = i;code = 105 char = i;code = 105 char = i;code = 105 char = );code = 41 char = ;code = 32 char = r;code = 114 char = e;code = 101 char = d;code = 100 char = u;code = 117 char = c;code = 99 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = f;code = 102 char = r;code = 114 char = e;code = 101 char = q;code = 113 char = u;code = 117 char = e;code = 101 char = n;code = 110 char = c;code = 99 char = y;code = 121 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = o;code = 111 char = p;code = 112 char = e;code = 101 char = n;code = 110 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = e;code = 101 char = v;code = 118 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = s;code = 115 char = ,;code = 44 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = m;code = 109 char = p;code = 112 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = b;code = 98 char = l;code = 108 char = e;code = 101 char = ;code = 32 char = w;code = 119 char = i;code = 105 char = t;code = 116 char = h;code = 104 char = ;code = 32 char = b;code = 98 char = o;code = 111 char = t;code = 116 char = h;code = 104 char = ;code = 32 char = i;code = 105 char = m;code = 109 char = p;code = 112 char = a;code = 97 char = i;code = 105 char = r;code = 114 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = o;code = 111 char = p;code = 112 char = e;code = 101 char = n;code = 110 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = s;code = 115 char = t;code = 116 char = a;code = 97 char = b;code = 98 char = i;code = 105 char = l;code = 108 char = i;code = 105 char = z;code = 122 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 = a;code = 97 char = ;code = 32 char = c;code = 99 char = l;code = 108 char = o;code = 111 char = s;code = 115 char = e;code = 101 char = d;code = 100 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 = 46 char = ;code = 32 char = I;code = 73 char = n;code = 110 char = ;code = 32 char = s;code = 115 char = u;code = 117 char = m;code = 109 char = m;code = 109 char = a;code = 97 char = r;code = 114 char = y;code = 121 char = ,;code = 44 char = ;code = 32 char = o;code = 111 char = u;code = 117 char = r;code = 114 char = ;code = 32 char = s;code = 115 char = t;code = 116 char = u;code = 117 char = d;code = 100 char = y;code = 121 char = ;code = 32 char = r;code = 114 char = e;code = 101 char = v;code = 118 char = e;code = 101 char = a;code = 97 char = l;code = 108 char = s;code = 115 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = a;code = 97 char = t;code = 116 char = ;code = 32 char = t;code = 116 char = r;code = 114 char = i;code = 105 char = c;code = 99 char = y;code = 121 char = c;code = 99 char = l;code = 108 char = i;code = 105 char = c;code = 99 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 = 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 = ;code = 32 char = h;code = 104 char = o;code = 111 char = m;code = 109 char = o;code = 111 char = m;code = 109 char = e;code = 101 char = r;code = 114 char = i;code = 105 char = c;code = 99 char = ;code = 32 char = C;code = 67 char = y;code = 121 char = s;code = 115 char = -;code = 45 char = l;code = 108 char = o;code = 111 char = o;code = 111 char = p;code = 112 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 = 32 char = b;code = 98 char = y;code = 121 char = ;code = 32 char = a;code = 97 char = c;code = 99 char = t;code = 116 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = r;code = 114 char = o;code = 111 char = u;code = 117 char = g;code = 103 char = h;code = 104 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 = ;code = 32 char = m;code = 109 char = e;code = 101 char = c;code = 99 char = h;code = 104 char = a;code = 97 char = n;code = 110 char = i;code = 105 char = s;code = 115 char = m;code = 109 char = s;code = 115 char = ;code = 32 char = a;code = 97 char = t;code = 116 char = ;code = 32 char = o;code = 111 char = p;code = 112 char = e;code = 101 char = n;code = 110 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = c;code = 99 char = l;code = 108 char = o;code = 111 char = s;code = 115 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = n;code = 110 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = m;code = 109 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = s;code = 115 char = t;code = 116 char = a;code = 97 char = t;code = 116 char = e;code = 101 char = s;code = 115 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = p;code = 112 char = r;code = 114 char = o;code = 111 char = b;code = 98 char = a;code = 97 char = b;code = 98 char = l;code = 108 char = y;code = 121 char = ;code = 32 char = a;code = 97 char = t;code = 116 char = ;code = 32 char = t;code = 116 char = w;code = 119 char = o;code = 111 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 = ;code = 32 char = d;code = 100 char = o;code = 111 char = m;code = 109 char = a;code = 97 char = i;code = 105 char = n;code = 110 char = s;code = 115 char = ,;code = 44 char = ;code = 32 char = n;code = 110 char = a;code = 97 char = m;code = 109 char = e;code = 101 char = l;code = 108 char = y;code = 121 char = ,;code = 44 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = p;code = 112 char = o;code = 111 char = r;code = 114 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 = o;code = 111 char = p;code = 112 char = e;code = 101 char = n;code = 110 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 = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = e;code = 101 char = x;code = 120 char = t;code = 116 char = r;code = 114 char = a;code = 97 char = c;code = 99 char = e;code = 101 char = l;code = 108 char = l;code = 108 char = u;code = 117 char = l;code = 108 char = a;code = 97 char = r;code = 114 char = ;code = 32 char = d;code = 100 char = o;code = 111 char = m;code = 109 char = a;code = 97 char = i;code = 105 char = n;code = 110 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 = c;code = 99 char = l;code = 108 char = o;code = 111 char = s;code = 115 char = e;code = 101 char = d;code = 100 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 = 46 char = <;code = 60 char = b;code = 98 char = r;code = 114 char = /;code = 47 char = >;code = 62 result sql = Tricyclic antidepressants not only inhibit monoamine reuptake but also modulate Cys-loop receptors. However, it is not understood how this modulation is involved in their therapeutic effects. We analyzed the mechanisms of inhibition of homomeric 5-HT(3A) and alpha7-5HT(3A) receptors by tricyclic antidepressants at the single-channel and macroscopic current levels. These drugs reduce agonist-evoked currents in a noncompetitive and concentration-dependent manner. When they act on the open state, the reduction is similar for both receptors and it is voltage-dependent, thus suggesting an open-channel block process in which the blocked channel can either close or remain stabilized. By acting on the resting state, tricyclic antidepressants reduce the peak current in a voltage-independent manner, with a potency 6-fold higher for 5-HT(3A) than for alpha7-5HT(3A) (IC(50): 6 microM and 1 microM for alpha7-5HT(3A) and 5-HT(3A), respectively). Thus, tricyclic antidepressants may act on closed channels at the unshared extracellular domain from where they inhibit channel opening. Single alpha7-5HT(3A) channels in the continued presence of tricyclic antidepressants show: i) reduced open durations, compatible with open-channel block; ii) reduced burst durations, compatible with closing of blocked channels; and iii) reduced frequency of opening events, compatible with both impaired opening and stabilization of a closed state. In summary, our study reveals that tricyclic antidepressants inhibit homomeric Cys-loop receptors by acting through different mechanisms at open and closed conformational states and probably at two different domains, namely, the pore in the open state and the extracellular domain in the closed state.
Publication: Eur. J. Pharmacol. 2008 Apr 14 ;584(1)::30-9. :doi: 10.1016/j.ejphar.2008.01.023.
Publication Date: 2008 Apr 14
Study Author(s): Gumilar, Fernanda;Bouzat, Cecilia;
Institution: Instituto de Investigaciones Bioquímicas, Universidad Nacional del Sur-CONICET, Camino La Carrindanga Km 7, B8000FWB, Bahía Blanca, Argentina.
Shortcut link to this study:
Tricyclic antidepressants not only inhibit monoamine reuptake but also modulate Cys-loop receptors. However, it is not understood how this modulation is involved in their therapeutic effects. We analyzed the mechanisms of inhibition of homomeric 5-HT(3A) and alpha7-5HT(3A) receptors by tricyclic antidepressants at the single-channel and macroscopic current levels. These drugs reduce agonist-evoked currents in a noncompetitive and concentration-dependent manner. When they act on the open state, the reduction is similar for both receptors and it is voltage-dependent, thus suggesting an open-channel block process in which the blocked channel can either close or remain stabilized. By acting on the resting state, tricyclic antidepressants reduce the peak current in a voltage-independent manner, with a potency 6-fold higher for 5-HT(3A) than for alpha7-5HT(3A) (IC(50): 6 microM and 1 microM for alpha7-5HT(3A) and 5-HT(3A), respectively). Thus, tricyclic antidepressants may act on closed channels at the unshared extracellular domain from where they inhibit channel opening. Single alpha7-5HT(3A) channels in the continued presence of tricyclic antidepressants show: i) reduced open durations, compatible with open-channel block; ii) reduced burst durations, compatible with closing of blocked channels; and iii) reduced frequency of opening events, compatible with both impaired opening and stabilization of a closed state. In summary, our study reveals that tricyclic antidepressants inhibit homomeric Cys-loop receptors by acting through different mechanisms at open and closed conformational states and probably at two different domains, namely, the pore in the open state and the extracellular domain in the closed state.
PMID: 18314100