Dopamine agonist 3-PPP fails to protect against MPTP-induced toxicity.
We investigated the neuroprotective effect of the dopamine agonist, 3-PPP [3-(3-hydroxyphenyl)-N-propylpiperidine] against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. MPTP (30 mg/kg, i.p., twice, 16 h apart) causes significant dopamine depletion in nucleus caudatus putamen (NCP) by 1 week. 3-PPP had no effect on the monoamine oxidase-B activity (MAO-B) activity in NCP. 3-PPP did not affect dopamine uptake, whereas mazindol significantly blocked the uptake of dopamine dose dependently. MPTP-induced behavioral changes in mice were not reduced by pretreatment with 3-PPP. This dopamine agonist did not prevent dopamine depletion caused by MPTP. MPP+ (20 microM) significantly inhibited the cell proliferation of SH-SY5Y dopaminergic neuronal cells. 3-PPP had no effect on the SH-SY5Y neuronal cell growth in culture and did not block the MPP(+)-induced cytotoxicity. This study shows that the dopamine agonist 3-PPP failed to protect against MPTP-induced dopaminergic neurotoxicity.
Department of Pharmacology, Physiology and Therapeutics, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota 58203, USA.
Dhanasekaran
D
Muralikrishnan
Manuchair
M
Ebadi
Holly M
HM
Brown-Borg
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002455:Cell Division; D045744:Cell Line, Tumor; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism / Q000493:pharmacokinetics; D018491:Dopamine Agonists / Q000494:pharmacology*; D006801:Humans; D020267:MPTP Poisoning / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control* / Q000523:psychology; D051379:Mice; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D017211:Treatment Failure
D018491:Dopamine Agonists; D018696:Neuroprotective Agents; D010880:Piperidines; C026539:preclamol; D008995:Monoamine Oxidase; D004298:Dopamine