1-Methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-methyl-MPTP) is less neurotoxic than MPTP in the common marmoset.
Four adult marmosets were treated with increasing doses of 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-methyl-MPTP) in the range 0.23-4.3 mg/kg i.p. to give a cumulative dose of 11.0-11.6 mg/kg over a 6-10 day period. After 4 days of treatment, and as the dosage was gradually increased, the animals exhibited mild motor deficits. These abnormalities slowly declined over the following 1-6 week period. In contrast, similar treatment of common marmosets with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (1-4 mg/kg i.p.) for 3-5 days in a cumulative dose of 6.9-9.2 mg/kg produced gross impairment of motor function which persisted throughout the 5 weeks period of observation. Administration of 2'-methyl-MPTP for 6-10 days caused some decrease in dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC), but not homovanillic acid (HVA) content in the caudate nucleus in animals 5-6 weeks after the start of treatment. There was a small decrease in [3H]dopamine uptake into putamen synaptosomes. This contrasted with the marked decreases in all these parameters observed after MPTP treatment of common marmosets. Histological examination of the substantia nigra from the four animals treated with 2'-methyl-MPTP did not show degeneration or loss of dopamine-containing cell bodies in the zona compacta. In contrast, MPTP caused severe destruction of these pigmented nigral neurones. In the common marmoset 2'-methyl-MPTP does not appear to show the same neurotoxic action as MPTP itself. This contrasts with findings in the mouse where 2'-methyl-MPTP is more toxic to dopamine-containing cells of substantia nigra than MPTP.
Rose
S
S
Parkinson's Disease Society Experimental Research Laboratories, Biomedical Sciences Division, King's College, London, U.K.
Nomoto
M
M
Jackson
E A
EA
Gibb
W R
WR
Jenner
P
P
Marsden
C D
CD
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000031:analogs & derivatives*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001679:Biogenic Amines / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D002143:Callitrichinae; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000502:physiology; D005260:Female; D020267:MPTP Poisoning; D008297:Male; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure
D001679:Biogenic Amines; C048977:1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine