Antiparkinsonian efficacy of a novel transdermal delivery system for (+)-PHNO in MPTP-treated squirrel monkeys

We examined the ability of the antiparkinsonian agent (+)-4-propyl-9-hydroxynaphthoxazine (PHNO) to enter the systemic circulation in therapeutic concentrations after continuous transdermal absorption in squirrel monkeys rendered parkinsonian by MPTP. Direct subcutaneous administration of (+)-PHNO in the dose range of 2.5 to 20 μg/kg restored locomotor activity to levels seen in normal monkeys for approximately 1 hour. Application of transdermal patches capable of delivering, into an infinite sink, an estimated 2.6 μg/cm 2 /h of (+ )-PHNO over a skin surface area of 4.78 to 19.12 cm 2 also restored locomotor activity to the normal range during a 24-hour period. We suggest the use of transdermal application of PHNO as a novel drug delivery system for the improved management of Parkinson9s disease.