Transdermal administration of piribedil reverses MPTP-induced motor deficits in the common marmoset

The ability of transdermal administration of the dopamine D2/D3 agonist pir ibedil (1-[3,4-methylenedioxybenzyl)]-4-[(2-pyrimidinyl)]piperazine) to rev erse hypokinesia and other motor deficits observed in MPTP-treated common m armosets was investigated. Piribedil (2.5-10.0 mg/animal), applied directly to the skin of the abdomen as a paste, produced a long-lasting and concent ration-dependent reversal of motor deficits. The antiparkinsonian actions o f piribedil occurred within 10 minutes of drug administration and lasted as long as 10 hours. Transdermally applied piribedil produced a pattern of lo comotor activity characteristic of normal motor behavior in this species. S ymptoms of nausea (marked excessive salivation, retching, and/or vomiting) were not observed after transdermal application of piribedil. Additionally, pretreatment with the peripheral dopamine antagonist domperidone enhanced the antiparkinsonian effects of piribedil. Application to the skin of monol ayer or bilayer patches impregnated with piribedil also produced a marked i ncrease in locomotor activity and reversal of motor deficits. After applica tion of various patch fractions (whole, one-half, or one-fourth), the incre ase in locomotor activity and reversal of disability correlated well with t he surface area of skin covered. Measurement of serum levels of piribedil a fter single application of bilayer patches showed a positive relationship b etween drug levels and antiparkinsonian activity. Repeated daily applicatio n of piribedil bilayer patches for 5 days to MPTP-treated common marmosets primed to show dyskinesia by previous exposure to L-Dopa produced antiparki nsonian activity accompanied by dyskinetic movements. Transdermal administr ation of dopamine agonists such as piribedil may provide a useful means of producing a long-lasting reversal of motor deficits in Parkinson's disease while avoiding acute adverse effects such as nausea.