Studies on the anti-dyskinesia effect of apomorphine in man

In man, central dopamine (DA) is thought to underlie the production of choreoathetotic movements (CAM) that occur in a variety of neurological disorders. We have reported that apomorphine (APOM), a direct DA receptor stimulant, attenuates CAM in man. To investigate the mechanism by which APOM diminishes dyskinesia, we administered levodopa (4.5-6 gm/day, up to 10 munths duration) and subsequently haloperidol, up to tolerated doses, to a group of patients afflicted with CAM of various etiologies in whom we first had observed lessening in CAM with injected APOM. Levodopa produced no consistent change in CAM and haloperidol effectively reduced the CAM in all patients. The effect of APOM, then, upon the dyskinesia in these patients, paralleled that of haloperdol, a strong DA receptor blocking agent. Cholinergic agents can attenuate CAM in man and it has been suggested that the anti-CAM effect of APOM is a cholinergic one, medicated through its tetrahydroisoquinoline or its piperidine monties. We administered physostigmine i.v. (1.0-2.0 mg) to six patients in whom APOM had been shown to antagonize their CAM. In only one case a moderate reduction in CAM was noted. It is concluded that the anti-dyskinetic effect of APOM is mediated by an anti-DA effect, which may result from direct stimulation of presynaptic DA receptors, which has been shown to reduce the impulse flow and release of DA from nerve endings of dopaminergic neurons or perhaps from the accumulation of an antidopaminergic metabolite on DA receptors.