Stereoselective reversal of MPTP-induced parkinsonism in the marmoset after dermal application of N-0437.
The selective dopamine D-2 receptor agonist N-0437 produced a rapid and dose-dependent reversal of motor deficits lasting 90-120 min following i.p. or oral administration of the racemate to MPTP-treated common marmosets. In contrast, topical application of (+/-)-, (+)- or (-)-N-0437 to the skin of MPTP-treated animals did not alter locomotor activity in the initial 4 h although other motor disabilities were reduced. However, 24 h following application of the racemate or the (-) enantiomer both locomotor activity and the other motor deficits induced by MPTP were improved. The increase in locomotor activity returned to basal values by 48-52 h following application of the racemate to the skin and by 72-76 h following administration of (-)-N-0437; the other motor deficits induced by MPTP were reduced for up to 72-76 h by both (+/-)- and (-)-N-0437. Application to skin of the (+) enantiomer produced no behavioural improvement or stimulation of locomotor activity. Transdermal administration of the active enantiomer of N-0437 may be of value in producing a prolonged reversal of parkinsonian motor deficits in man.
Löschmann
P A
PA
Research Laboratories of Schering AG, Berlin, F.R.G.
Chong
P N
PN
Nomoto
M
M
Tepper
P G
PG
Horn
A S
AS
Jenner
P
P
Marsden
C D
CD
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000287:Administration, Topical; D000818:Animals; D002143:Callitrichinae; D015259:Dopamine Agents / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced*; D013237:Stereoisomerism; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000494:pharmacology*; D013876:Thiophenes / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D015259:Dopamine Agents; D009281:Naphthalenes; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C047508:rotigotine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine