char = T;code = 84 char = a;code = 97 char = r;code = 114 char = g;code = 103 char = e;code = 101 char = t;code = 116 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = a;code = 97 char = c;code = 99 char = u;code = 117 char = t;code = 116 char = e;code = 101 char = ;code = 32 char = i;code = 105 char = s;code = 115 char = c;code = 99 char = h;code = 104 char = e;code = 101 char = m;code = 109 char = i;code = 105 char = c;code = 99 char = ;code = 32 char = s;code = 115 char = t;code = 116 char = r;code = 114 char = o;code = 111 char = k;code = 107 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 = a;code = 97 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 = 45 char = s;code = 115 char = e;code = 101 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 char = ;code = 32 char = o;code = 111 char = p;code = 112 char = e;code = 101 char = n;code = 110 char = e;code = 101 char = r;code = 114 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = m;code = 109 char = a;code = 97 char = x;code = 120 char = i;code = 105 char = -;code = 45 char = K;code = 75 char = ;code = 32 char = p;code = 112 char = o;code = 111 char = t;code = 116 char = a;code = 97 char = s;code = 115 char = s;code = 115 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 = s;code = 115 char = .;code = 46 result sql = Targeting acute ischemic stroke with a calcium-sensitive opener of maxi-K potassium channels.
Targeting acute ischemic stroke with a calcium-sensitive opener of maxi-K potassium channels.char = D;code = 68 char = u;code = 117 char = r;code = 114 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = i;code = 105 char = s;code = 115 char = c;code = 99 char = h;code = 104 char = e;code = 101 char = m;code = 109 char = i;code = 105 char = c;code = 99 char = ;code = 32 char = s;code = 115 char = t;code = 116 char = r;code = 114 char = o;code = 111 char = k;code = 107 char = e;code = 101 char = ,;code = 44 char = ;code = 32 char = n;code = 110 char = e;code = 101 char = u;code = 117 char = r;code = 114 char = o;code = 111 char = n;code = 110 char = s;code = 115 char = ;code = 32 char = a;code = 97 char = t;code = 116 char = ;code = 32 char = r;code = 114 char = i;code = 105 char = s;code = 115 char = k;code = 107 char = ;code = 32 char = a;code = 97 char = r;code = 114 char = e;code = 101 char = ;code = 32 char = e;code = 101 char = x;code = 120 char = p;code = 112 char = o;code = 111 char = s;code = 115 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = t;code = 116 char = o;code = 111 char = ;code = 32 char = p;code = 112 char = a;code = 97 char = t;code = 116 char = h;code = 104 char = o;code = 111 char = l;code = 108 char = o;code = 111 char = g;code = 103 char = i;code = 105 char = c;code = 99 char = a;code = 97 char = l;code = 108 char = l;code = 108 char = y;code = 121 char = ;code = 32 char = h;code = 104 char = i;code = 105 char = g;code = 103 char = h;code = 104 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 = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = i;code = 105 char = n;code = 110 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 = 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 = (;code = 40 char = C;code = 67 char = a;code = 97 char = +;code = 43 char = +;code = 43 char = );code = 41 char = ,;code = 44 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = i;code = 105 char = t;code = 116 char = i;code = 105 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = a;code = 97 char = ;code = 32 char = f;code = 102 char = a;code = 97 char = t;code = 116 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = b;code = 98 char = i;code = 105 char = o;code = 111 char = c;code = 99 char = h;code = 104 char = e;code = 101 char = m;code = 109 char = i;code = 105 char = c;code = 99 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = c;code = 99 char = a;code = 97 char = s;code = 115 char = c;code = 99 char = a;code = 97 char = d;code = 100 char = e;code = 101 char = .;code = 46 char = ;code = 32 char = T;code = 84 char = o;code = 111 char = ;code = 32 char = p;code = 112 char = r;code = 114 char = o;code = 111 char = t;code = 116 char = e;code = 101 char = c;code = 99 char = t;code = 116 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = s;code = 115 char = e;code = 101 char = ;code = 32 char = n;code = 110 char = e;code = 101 char = u;code = 117 char = r;code = 114 char = o;code = 111 char = n;code = 110 char = s;code = 115 char = ,;code = 44 char = ;code = 32 char = w;code = 119 char = e;code = 101 char = ;code = 32 char = h;code = 104 char = a;code = 97 char = v;code = 118 char = e;code = 101 char = ;code = 32 char = d;code = 100 char = e;code = 101 char = v;code = 118 char = e;code = 101 char = l;code = 108 char = o;code = 111 char = p;code = 112 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 = e;code = 101 char = r;code = 114 char = s;code = 115 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = l;code = 108 char = a;code = 97 char = r;code = 114 char = g;code = 103 char = e;code = 101 char = -;code = 45 char = c;code = 99 char = o;code = 111 char = n;code = 110 char = d;code = 100 char = u;code = 117 char = c;code = 99 char = t;code = 116 char = a;code = 97 char = n;code = 110 char = c;code = 99 char = e;code = 101 char = ,;code = 44 char = ;code = 32 char = C;code = 67 char = a;code = 97 char = +;code = 43 char = +;code = 43 char = -;code = 45 char = a;code = 97 char = c;code = 99 char = t;code = 116 char = i;code = 105 char = v;code = 118 char = a;code = 97 char = t;code = 116 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = (;code = 40 char = m;code = 109 char = a;code = 97 char = x;code = 120 char = i;code = 105 char = -;code = 45 char = K;code = 75 char = ;code = 32 char = o;code = 111 char = r;code = 114 char = ;code = 32 char = B;code = 66 char = K;code = 75 char = );code = 41 char = ;code = 32 char = p;code = 112 char = o;code = 111 char = t;code = 116 char = a;code = 97 char = s;code = 115 char = s;code = 115 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 = s;code = 115 char = ,;code = 44 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = r;code = 114 char = e;code = 101 char = b;code = 98 char = y;code = 121 char = ;code = 32 char = a;code = 97 char = u;code = 117 char = g;code = 103 char = m;code = 109 char = e;code = 101 char = n;code = 110 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 = e;code = 101 char = n;code = 110 char = d;code = 100 char = o;code = 111 char = g;code = 103 char = e;code = 101 char = n;code = 110 char = o;code = 111 char = u;code = 117 char = s;code = 115 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 = ;code = 32 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = ;code = 32 char = r;code = 114 char = e;code = 101 char = g;code = 103 char = u;code = 117 char = l;code = 108 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = C;code = 67 char = a;code = 97 char = +;code = 43 char = +;code = 43 char = ;code = 32 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = r;code = 114 char = y;code = 121 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = m;code = 109 char = e;code = 101 char = m;code = 109 char = b;code = 98 char = r;code = 114 char = a;code = 97 char = n;code = 110 char = e;code = 101 char = ;code = 32 char = p;code = 112 char = o;code = 111 char = t;code = 116 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = i;code = 105 char = a;code = 97 char = l;code = 108 char = .;code = 46 char = ;code = 32 char = T;code = 84 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = n;code = 110 char = o;code = 111 char = v;code = 118 char = e;code = 101 char = l;code = 108 char = ;code = 32 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 = -;code = 45 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 = s;code = 115 char = ;code = 32 char = B;code = 66 char = M;code = 77 char = S;code = 83 char = -;code = 45 char = 2;code = 50 char = 0;code = 48 char = 4;code = 52 char = 3;code = 51 char = 5;code = 53 char = 2;code = 50 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = r;code = 114 char = a;code = 97 char = c;code = 99 char = e;code = 101 char = m;code = 109 char = i;code = 105 char = c;code = 99 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = m;code = 109 char = p;code = 112 char = o;code = 111 char = u;code = 117 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = 1;code = 49 char = ;code = 32 char = a;code = 97 char = r;code = 114 char = e;code = 101 char = ;code = 32 char = p;code = 112 char = o;code = 111 char = t;code = 116 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = ,;code = 44 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 = 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 = u;code = 117 char = n;code = 110 char = i;code = 105 char = q;code = 113 char = u;code = 117 char = e;code = 101 char = l;code = 108 char = y;code = 121 char = ;code = 32 char = C;code = 67 char = a;code = 97 char = +;code = 43 char = +;code = 43 char = -;code = 45 char = s;code = 115 char = e;code = 101 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 char = ;code = 32 char = o;code = 111 char = p;code = 112 char = e;code = 101 char = n;code = 110 char = e;code = 101 char = r;code = 114 char = s;code = 115 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = m;code = 109 char = a;code = 97 char = x;code = 120 char = i;code = 105 char = -;code = 45 char = K;code = 75 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 = 46 char = ;code = 32 char = I;code = 73 char = n;code = 110 char = ;code = 32 char = r;code = 114 char = a;code = 97 char = t;code = 116 char = ;code = 32 char = m;code = 109 char = o;code = 111 char = d;code = 100 char = e;code = 101 char = l;code = 108 char = s;code = 115 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = p;code = 112 char = e;code = 101 char = r;code = 114 char = m;code = 109 char = a;code = 97 char = n;code = 110 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = ;code = 32 char = l;code = 108 char = a;code = 97 char = r;code = 114 char = g;code = 103 char = e;code = 101 char = -;code = 45 char = v;code = 118 char = e;code = 101 char = s;code = 115 char = s;code = 115 char = e;code = 101 char = l;code = 108 char = ;code = 32 char = s;code = 115 char = t;code = 116 char = r;code = 114 char = o;code = 111 char = k;code = 107 char = e;code = 101 char = ,;code = 44 char = ;code = 32 char = B;code = 66 char = M;code = 77 char = S;code = 83 char = -;code = 45 char = 2;code = 50 char = 0;code = 48 char = 4;code = 52 char = 3;code = 51 char = 5;code = 53 char = 2;code = 50 char = ;code = 32 char = p;code = 112 char = r;code = 114 char = o;code = 111 char = v;code = 118 char = i;code = 105 char = d;code = 100 char = e;code = 101 char = d;code = 100 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 = 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 = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = r;code = 114 char = t;code = 116 char = i;code = 105 char = c;code = 99 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = n;code = 110 char = e;code = 101 char = u;code = 117 char = r;code = 114 char = o;code = 111 char = p;code = 112 char = r;code = 114 char = o;code = 111 char = t;code = 116 char = e;code = 101 char = c;code = 99 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = w;code = 119 char = h;code = 104 char = e;code = 101 char = n;code = 110 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 = e;code = 101 char = r;code = 114 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = t;code = 116 char = w;code = 119 char = o;code = 111 char = ;code = 32 char = h;code = 104 char = o;code = 111 char = u;code = 117 char = r;code = 114 char = s;code = 115 char = ;code = 32 char = a;code = 97 char = f;code = 102 char = t;code = 116 char = e;code = 101 char = r;code = 114 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = o;code = 111 char = n;code = 110 char = s;code = 115 char = e;code = 101 char = t;code = 116 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = o;code = 111 char = c;code = 99 char = c;code = 99 char = l;code = 108 char = u;code = 117 char = s;code = 115 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ,;code = 44 char = ;code = 32 char = b;code = 98 char = u;code = 117 char = t;code = 116 char = ;code = 32 char = h;code = 104 char = a;code = 97 char = d;code = 100 char = ;code = 32 char = n;code = 110 char = o;code = 111 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 = n;code = 110 char = ;code = 32 char = b;code = 98 char = l;code = 108 char = o;code = 111 char = o;code = 111 char = d;code = 100 char = ;code = 32 char = p;code = 112 char = r;code = 114 char = e;code = 101 char = s;code = 115 char = s;code = 115 char = u;code = 117 char = r;code = 114 char = e;code = 101 char = ;code = 32 char = o;code = 111 char = r;code = 114 char = ;code = 32 char = c;code = 99 char = e;code = 101 char = r;code = 114 char = e;code = 101 char = b;code = 98 char = r;code = 114 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = b;code = 98 char = l;code = 108 char = o;code = 111 char = o;code = 111 char = d;code = 100 char = ;code = 32 char = f;code = 102 char = l;code = 108 char = o;code = 111 char = w;code = 119 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 = n;code = 110 char = o;code = 111 char = v;code = 118 char = e;code = 101 char = l;code = 108 char = ;code = 32 char = a;code = 97 char = p;code = 112 char = p;code = 112 char = r;code = 114 char = o;code = 111 char = a;code = 97 char = c;code = 99 char = h;code = 104 char = ;code = 32 char = m;code = 109 char = a;code = 97 char = y;code = 121 char = ;code = 32 char = r;code = 114 char = e;code = 101 char = s;code = 115 char = t;code = 116 char = r;code = 114 char = i;code = 105 char = c;code = 99 char = t;code = 116 char = ;code = 32 char = C;code = 67 char = a;code = 97 char = +;code = 43 char = +;code = 43 char = ;code = 32 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = r;code = 114 char = y;code = 121 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = n;code = 110 char = e;code = 101 char = u;code = 117 char = r;code = 114 char = o;code = 111 char = n;code = 110 char = s;code = 115 char = ;code = 32 char = a;code = 97 char = t;code = 116 char = ;code = 32 char = r;code = 114 char = i;code = 105 char = s;code = 115 char = k;code = 107 char = ;code = 32 char = w;code = 119 char = h;code = 104 char = i;code = 105 char = l;code = 108 char = e;code = 101 char = ;code = 32 char = h;code = 104 char = a;code = 97 char = v;code = 118 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = m;code = 109 char = i;code = 105 char = n;code = 110 char = i;code = 105 char = m;code = 109 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = s;code = 115 char = i;code = 105 char = d;code = 100 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 = s;code = 115 char = .;code = 46 char = <;code = 60 char = b;code = 98 char = r;code = 114 char = /;code = 47 char = >;code = 62 result sql = During ischemic stroke, neurons at risk are exposed to pathologically high levels of intracellular calcium (Ca++), initiating a fatal biochemical cascade. To protect these neurons, we have developed openers of large-conductance, Ca++-activated (maxi-K or BK) potassium channels, thereby augmenting an endogenous mechanism for regulating Ca++ entry and membrane potential. The novel fluoro-oxindoles BMS-204352 and racemic compound 1 are potent, effective and uniquely Ca++-sensitive openers of maxi-K channels. In rat models of permanent large-vessel stroke, BMS-204352 provided significant levels of cortical neuroprotection when administered two hours after the onset of occlusion, but had no effects on blood pressure or cerebral blood flow. This novel approach may restrict Ca++ entry in neurons at risk while having minimal side effects.
Publication: Nat. Med. 2001 Apr ;7(4)::471-7.
Publication Date: 2001 Apr
Study Author(s): Gribkoff, V K;Starrett, J E;Dworetzky, S I;Hewawasam, P;Boissard, C G;Cook, D A;Frantz, S W;Heman, K;Hibbard, J R;Huston, K;Johnson, G;Krishnan, B S;Kinney, G G;Lombardo, L A;Meanwell, N A;Molinoff, P B;Myers, R A;Moon, S L;Ortiz, A;Pajor, L;Pieschl, R L;Post-Munson, D J;Signor, L J;Srinivas, N;Taber, M T;Thalody, G;Trojnacki, J T;Wiener, H;Yeleswaram, K;Yeola, S W;
Institution: Neuroscience Drug Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut, USA.
[email protected]
Shortcut link to this study:
During ischemic stroke, neurons at risk are exposed to pathologically high levels of intracellular calcium (Ca++), initiating a fatal biochemical cascade. To protect these neurons, we have developed openers of large-conductance, Ca++-activated (maxi-K or BK) potassium channels, thereby augmenting an endogenous mechanism for regulating Ca++ entry and membrane potential. The novel fluoro-oxindoles BMS-204352 and racemic compound 1 are potent, effective and uniquely Ca++-sensitive openers of maxi-K channels. In rat models of permanent large-vessel stroke, BMS-204352 provided significant levels of cortical neuroprotection when administered two hours after the onset of occlusion, but had no effects on blood pressure or cerebral blood flow. This novel approach may restrict Ca++ entry in neurons at risk while having minimal side effects.