EFFECTS OF SEVERAL PARTIAL DOPAMINE D2 RECEPTOR AGONISTS IN CEBUS-APELLA MONKEYS PREVIOUSLY TREATED WITH HALOPERIDOL

Eight Cebus apella monkeys were treated with haloperidol for 2 years. Five monkeys had developed mild oral tardive dyskinesia and all were p rimed for neuroleptic induced dystonia, thus serving as a model for bo th chronic and acute extrapyramidal side effects. In this model, the p artial dopamine D2 receptor agonists SDZ HDC-912, SDZ HAC-911, terguri de, (-)-3-(3-hydroxyphenyl)-N-propylpiperidine) ((-)-3-PPP) and SND 91 9 were tested for extrapyramidal side-effect liability. Their antipsyc hotic potential was also tested, using a dose of dextroamphetamine pro ducing mild stereotypy and moderate motoric unrest. For comparison, th e dopamine D2 receptor agonist, LY 171555 and antagonist, raclopride w ere used. In contrast to the other drugs tested, SDZ HAC-911 consisten tly reduced oral activity, P < 0.05 (at doses from 0.005 to 0.025 mg/k g). The relative dystonic potencies were raclopride > SDZ HDC-912 > SD Z HAC-911 = terguride. Neither (-)-3-PPP nor SND 919 produced dystonia , but had observable dopamine D2 receptor agonistic effects, (-)-3-PPP producing emesis at 1-4 mg/kg and SND 919 producing motoric unrest an d stereotypy at 0.05-0.25 mg/kg. Comparing the antiamphetamine effects of the more antagonist-like drugs with raclopride, the relative poten cies were terguride = SDZ HAC-911 > SDZ HDC-912 > raclopride. Comparin g the antiamphetamine effects of the more agonist-like drugs with LY 1 71555, the relative potencies were SND 919 > (-)-3-PPP > LY 171555 in relation to motoric unrest, while neither (-)-3-PPP nor LY 171555 prod uced inhibition of stereotypy.