Kalkman H O, Neumann V, Nozulak J, Tricklebank M D
Nervous System Research, Novartis Pharma Inc., Basel, Switzerland.
Eur J Pharmacol. 1998 Feb 19;343(2-3):201-7. doi: 10.1016/s0014-2999(97)01554-9.
5-HT receptor antagonists with selectivity for 5-HT1A WAY-100635 (N-[2-[-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohe xanecarboxamide), 5-HT1B GR 127935 (N-[methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'(5-methyl-1,2, 4-oxadiazol-3-yl)[1,1-biphenyl]-4-carboxamide x HCl), 5-HT2C SB 200646A (N-(1-methyl-5-indolyl)-N'-(3-pyridyl)urea x HCl) and 5-HT2A (ketanserin, fananserin and MDL 100,151 ((+/-)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-pipe ridinemethanol) receptors were tested for cataleptogenic responses in rats. WAY-100635 (0.1-3 mg/kg, s.c.), ketanserin (0.1-3 mg/kg, s.c.), MDL 100,151 (0.3-3 mg/kg, s.c.) and fananserin (RP 62203; 3 mg/kg, s.c.) induced a significant catalepsy. GR 127935 (1 mg/kg, s.c.), SB 200646A (without effect per se at 10 mg/kg, s.c.) and MDL 100,151 (0.3 mg/kg, s.c.) did not inhibit the cataleptic response to the dopamine D2 receptor antagonist, loxapine (0.3 mg/kg, s.c.). Catalepsy induced by MDL 100,151 (3 mg/kg) was blocked by co-treatment with clozapine, but not by SB 200646A (both at 10 mg/kg, s.c.). Although clozapine displays significant affinity to 5-HT1A, 5-HT1B, 5-HT2A and 5-HT2C receptors, the present results suggest that blockade of these receptors is not responsible for clozapine's anticataleptic activity.
对5-HT1A（WAY-100635，N-[2-[-(2-甲氧基苯基)-1-哌嗪基]乙基]-N-(2-吡啶基)环己烷甲酰胺）、5-HT1B（GR 127935，N-[3-(4-甲基-1-哌嗪基)甲氧基苯基]-2'-甲基-4'(5-甲基-1,2,4-恶二唑-3-基)[1,1-联苯]-4-甲酰胺盐酸盐）、5-HT2C（SB 200646A，N-(1-甲基-5-吲哚基)-N'-(3-吡啶基)脲盐酸盐）和5-HT2A（酮色林、法南色林和MDL 100,151，(+/-)-α-(2,3-二甲氧基苯基)-1-[2-(4-氟苯基)乙基]-4-哌啶甲醇）受体具有选择性的5-羟色胺受体拮抗剂，在大鼠中进行了僵住反应测试。WAY-100635（0.1 - 3毫克/千克，皮下注射）、酮色林（0.1 - 3毫克/千克，皮下注射）、MDL 100,151（0.3 - 3毫克/千克，皮下注射）和法南色林（RP 62203；3毫克/千克，皮下注射）诱导出显著的僵住。GR 127935（1毫克/千克，皮下注射）、SB 200646A（皮下注射10毫克/千克时本身无作用）和MDL 100,151（0.3毫克/千克，皮下注射）未抑制对多巴胺D2受体拮抗剂洛沙平（0.3毫克/千克，皮下注射）的僵住反应。MDL 100,151（3毫克/千克）诱导的僵住可被与氯氮平联合治疗阻断，但不能被SB 200646A阻断（两者均为皮下注射10毫克/千克）。尽管氯氮平对5-HT1A、5-HT1B、5-HT2A和5-HT2C受体显示出显著亲和力，但目前的结果表明，阻断这些受体并非氯氮平抗僵住活性的原因。
