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

Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, England (Drs. Rupniak, Iversen, and Stahl, and S.J. Tye and C.A. Jennings)
Merck Institute for Therapeutic Research, Merck Sharp and Dohme Research Laboratories, West Point, PA. (Drs. Loper, Bondi, and Hichens, and E. Hand)

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/cm²/h of (+ )-PHNO over a skin surface area of 4.78 to 19.12 cm² 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 Parkinson's disease.

Address correspondence and reprint requests to Dr. Rupniak, Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex, CM20 2QR, England.

Received July 22, 1988. Accepted for publication in final form September 6, 1988.

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