benztropine and amfonelic-acid

Electrical stimulation of the median forebrain bundle evoked dopamine release in the ipsilateral striatum which was monitored with high-speed cyclic voltammetry. After stimulation, the extracellular concentration of dopamine fell due to uptake in a biphasic manner, showing zero-order and first-order components. The zero-order phase corresponded to a Vmax of 42.8 +/- 1.8 nmol/min/g tissue. The uptake system could be blocked by D-amphetamine, methylphenidate and nomifensine, but not by benztropine, amfonelic acid or mazindol. The density of uptake sites showed a correlation with the density of striatal dopamine innervation.

Topics: Animals; Benztropine; Corpus Striatum; Dextroamphetamine; Dopamine; Electric Stimulation; Male; Mazindol; Medial Forebrain Bundle; Methylphenidate; Nalidixic Acid; Naphthyridines; Neural Pathways; Nomifensine; Rats; Rats, Inbred Strains

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a recently described neurotoxin, produces a marked dopamine (DA) depletion in the mouse striatum. In this study, a series of DA uptake blockers was tested for their ability to prevent this effect of MPTP. The agents tested (amfonelic acid, benztropine, bupropion and mazindol) completely protected against DA depletion in the mouse striatum when given before DA-depleting doses of MPTP were administered, whereas atropine and trihexyphenidyl (which were employed for comparative purposes) did not. DA uptake blocking agents appear to represent a second general class of compounds, monoamine oxidase inhibitors being the first, which protect against the biologic effects of MPTP in the mouse.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Benztropine; Bupropion; Corpus Striatum; Dopamine; Male; Mazindol; Mice; Mice, Inbred C57BL; Nalidixic Acid; Naphthyridines; Parasympatholytics; Propiophenones; Pyridines; Receptors, Dopamine