NMDA receptor antagonists inhibit catalepsy induced by either dopamine D1 or D2 receptor antagonists.
In the present study, we investigated the ability of NMDA receptor antagonists to inhibit catalepsy induced by haloperidol, or SCH23390 and clebopride, selective dopamine D1 and D2 receptor antagonists respectively. Catalepsy was measured by recording the time the animal remained with its forepaws placed over a rod 6 cm above the bench. Pretreatment with either the non-competitive NMDA receptor antagonist, MK-801 (0.25-0.5 mg/kg i.p.) or the competitive antagonist, LY274614 (10-20 mg/kg i.p.) reduced the cataleptic response produced by haloperidol (10 mg/kg), SCH23390 (2.5-10 mg/kp i.p.) or clebopride (5-20 mg/kg i.p.). This demonstrates that NMDA receptor antagonists will reduce both dopamine D1 and D2 receptor antagonist-induced catalepsy. Muscle relaxant doses of chlordiazepoxide (10 mg/kg i.p.) failed to reduce the catalepsy induced by haloperidol, suggesting that the anticataleptic effect of the NMDA receptor antagonists was not due to a non-specific action. These results support the hypothesis that NMDA receptor antagonists may have beneficial effects in disorders involving reduced dopaminergic function, such as Parkinson's disease.
Moore
N A
NA
Lilly Research Centre, Eli Lilly and Co., Windlesham, Surrey, UK.
Blackman
A
A
Awere
S
S
Leander
J D
JD
D000818:Animals; D001549:Benzamides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001552:Benzazepines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002375:Catalepsy / Q000139:chemically induced / Q000517:prevention & control*; D002707:Chlordiazepoxide / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D006220:Haloperidol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D001549:Benzamides; D001552:Benzazepines; D065127:Dopamine D2 Receptor Antagonists; D007546:Isoquinolines; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; C070935:LY 274614; D016291:Dizocilpine Maleate; D002707:Chlordiazepoxide; C014417:clebopride; D006220:Haloperidol