The role of coronary perfusion changes in cardiac dysfunction associated with brain death

The contribution of dopamine D1 receptor stimulation to the motor effects of dopaminergic drugs in patients with Parkinson's disease remains undetermined. The authors of this article studied the clinical efficacy, pharmacokinetics, and tolerability of the full D1 receptor agonist dihydrexidine, (+/-)-trans-10,11-dihydroxy-5,6,6a,7,8,12b-hexahydrobenzoa] phenanthridine hydrochloride in a double-blind, placebo-controlled trial in four patients with Parkinson's disease. Single intravenous doses were carefully titrated according to a fixed schedule ranging from 2 mg to the highest tolerated dose (or a maximum of 70 mg) infused over either 15 or 120 minutes. The only patient to achieve a plasma drug concentration greater than 100 ng/ml had a brief but definite motor improvement accompanied by choreic dyskinesias similar to the response to levodopa. Dose-limiting adverse effects, including flushing, hypotension, and tachycardia, were observed in all cases, especially with rapid infusions. No nausea or emesis occurred. Pharmacokinetic studies yielded a plasma half-life < 5 minutes. These preliminary data suggest that dihydrexidine has a marginal therapeutic window for providing an antiparkinsonian effect, although it remains uncertain how much of this effect is attributable to pure D1 receptor stimulation.