Inhibition of dopamine uptake by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a cause of parkinsonism.
N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine has been reported to cause parkinsonism in man and monkeys, producing behavioral effects within 5 min of administration. The compound reversibly and competively inhibited (IC50 = 2 microM) dopamine uptake into PC12, a clonal line of rat pheochromocytoma cells that store and secrete dopamine and acetylcholine. Uptake of choline and 2-deoxyglucose was not affected. Prolonged exposure to the compound was lethal to PC12; survivors of this treatment lost the ability to store dopamine and acetylcholine and to extend neurites upon incubation with nerve growth factor.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000310:Adrenal Gland Neoplasms / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D004298:Dopamine / Q000378:metabolism*; D007700:Kinetics; D010302:Parkinson Disease, Secondary / Q000139:chemically induced; D010673:Pheochromocytoma / Q000378:metabolism*; D011725:Pyridines / Q000633:toxicity*; D051381:Rats
D011725:Pyridines; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine