The selective dopamine D3 receptor antagonists, SB 277011-A and S 33084 block haloperidol-induced catalepsy in rats.
SB 277011-A (trans-N-[4-[2-(6-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-4-quinolinecarboxamide) and S 33084 [(3aR,9bS)-N[4-(8-cyano-1,3a,4,9b-tetrahydro-3H-benzopyrano[3,4-c]pyrrole-2-yl)-butyl](4-phenyl)benzamide] were already shown to lack cataleptogenic actions. Further to that, we report that SB 277011 exerted a dose-dependent dampening on the development of haloperidol-induced catalepsy in the dose-range of 13.5-30 mg/kg p.o. while S 33084, at the dose of 0.625 mg/kg sc. significantly inhibited catalepsy induced by haloperidol; had no effect at 1.25 mg/kg, and further augmented the effect of haloperidol after 2.5 mg/kg. The compounds also produced effective inhibition when administered 2 hours after haloperidol. The results underline that dopamine D3 receptor antagonist action may have therapeutic value in the treatment of schizophrenia.
Gyertyán
István
I
Department of Behavioural Pharmacology, Gedeon Richter Plc., Budapest, Hungary. i.gyertyan@richter.hu
Sághy
Katalin
K
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002375:Catalepsy / Q000139:chemically induced / Q000188:drug therapy*; D006220:Haloperidol; D008297:Male; D009570:Nitriles / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors*; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*
D001578:Benzopyrans; D009570:Nitriles; D011758:Pyrroles; D050637:Receptors, Dopamine D3; C408389:S 33084; C409982:SB 277011; D044005:Tetrahydroisoquinolines; D006220:Haloperidol