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 micrograms/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 micrograms/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.
Rupniak
N M
NM
Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, England.
Tye
S J
SJ
Jennings
C A
CA
Loper
A E
AE
Bondi
J V
JV
Hichens
M
M
Hand
E
E
Iversen
S D
SD
Stahl
S M
SM
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000279:Administration, Cutaneous; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000097:blood; D001522:Behavior, Animal / Q000187:drug effects; D008297:Male; D010078:Oxazines / Q000008:administration & dosage* / Q000097:blood; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy*; D011725:Pyridines; D012453:Saimiri
D000978:Antiparkinson Agents; D010078:Oxazines; D011725:Pyridines; C042631:naxagolide; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine