A Parkinson-like neurologic deficit in primates is caused by a novel 4-substituted piperidine.
A neurologic deficit characterized by hypokinesia, postural flexion, and to a lesser extent, rigidity, tremor and myoclonus, has been observed in cynomolgus monkeys following administration of 1-methyl-4-(1-methylpyrrol-2-yl)-4-piperidinol (MMPP), a novel 4-substituted piperidine. The syndrome, similar to that described for 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), developed within 3-7 days after oral or i.v. dosing, and was accompanied by lesions in the substantia nigra. The behavioral syndrome was seen to a lesser extent in dogs but not in rats. MMPP contains a hydroxyl group on the 4-position of the pyridine ring; the corresponding dehydration product was inactive.
Wilkening
D
D
Vernier
V G
VG
Arthaud
L E
LE
Treacy
G
G
Kenney
J P
JP
Nickolson
V J
VJ
Clark
R
R
Smith
D H
DH
Smith
C
C
Boswell
G
G
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D008252:Macaca fascicularis; D008297:Male; D009498:Neurotoxins / Q000008:administration & dosage / Q000633:toxicity*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D010545:Peroxides / Q000008:administration & dosage / Q000633:toxicity*; D010795:Phthalic Acids; D051381:Rats; D011919:Rats, Inbred Strains; D013378:Substantia Nigra / Q000187:drug effects
D009498:Neurotoxins; D010545:Peroxides; D010795:Phthalic Acids; C044731:magnesium monoperoxyphthalate