Eight Cebus apella monkeys were treated with
haloperidol for 2 years. Five monkeys had developed mild oral
tardive dyskinesia and all were primed for
neuroleptic induced
dystonia, thus serving as a model for both chronic and acute extrapyramidal side effects. In this model, the partial
dopamine D2 receptor agonists SDZ HDC-912, SDZ HAC-911,
terguride, (-)-3-(3-hydroxyphenyl)-N-propylpiperidine) ((-)-3-PPP) and
SND 919 were tested for extrapyramidal side-effect liability. Their
antipsychotic potential was also tested, using a dose of
dextroamphetamine producing mild stereotypy and moderate motoric unrest. For comparison, the
dopamine D2 receptor agonist,
LY 171555 and antagonist,
raclopride were used. In contrast to the other drugs tested, SDZ HAC-911 consistently reduced oral activity, P < 0.05 (at doses from 0.005 to 0.025 mg/kg). The relative dystonic potencies were
raclopride >
SDZ HDC-912 > SDZ 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 and stereotypy at 0.05-0.25 mg/kg. Comparing the antiamphetamine effects of the more antagonist-like drugs with
raclopride, the relative potencies were
terguride = SDZ HAC-911 >
SDZ HDC-912 >
raclopride. Comparing the antiamphetamine effects of the more agonist-like drugs with
LY 171555, the relative potencies were
SND 919 > (-)-3-PPP >
LY 171555 in relation to motoric unrest, while neither (-)-3-PPP nor
LY 171555 produced inhibition of stereotypy.