CATALEPTOGENIC EFFECT OF SUBTYPE-SELECTIVE 5-HT RECEPTOR ANTAGONISTS IN THE RAT

5-HT receptor antagonists with selectivity for 5-HT1A WAY-100635 nyl]e thyl]-N-(2-pyridinyl)cyclohexanecarboxamide), 5-HT1B GR 127935 -1,2,4- oxadiazol-3-yl)[1,1-biphenyl]-4-carboxamide . HCl), 5-HT2C SB 200646A (N-(1-methyl-5-indolyl)-N'-(3-pyridyl)urea . HCl) and 5-HT2A (ketanser in, fananserin and MDL 100,151(1) -1-[2-(4-fluorophenyl)ethyl]-4-piper idinemethanol) receptors were tested for cataleptogenic responses in r ats. WAY-100635 (0.1-3 mg/kg, s.c.), ketanserin (0.1-3 mg/kg, s.c.), M DL 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 20064 6A (without effect per se at 10 mg/kg, s.c.) and MDL 100,151 (0.3 mg/k g, s.c.) did not inhibit the cataleptic response io the dopamine D-2 r eceptor antagonist, loxapine (0.3 mg/kg, s.c.). Catalepsy induced by M DL 100,151 (3 mg/kg) was blocked by co-treatment with clozapine, but n ot 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 re sponsible for clozapine's anticataleptic activity. (C) 1998 Elsevier S cience B.V.