The inhibitory effect of certain centrally acting drugs, including antiparkinsonian agents, tricyclic antidepressant and phenothiazine, was studied
in vitro on the accumulation of dopamine into a crude mitochondrial fraction (P
2-fraction) from rat striatal homogenate, and the site of inhibition was studied by further fractionating the P
2-fraction into synaptic vesicles fraction (P
2V-fraction) and supernatant fluid (P
2S-fraction). Many antiparkinsonian agents, such as benztropine, trihexyphenidyl, ethopropazine, diphenhydramine or 6, 6, 9-trimethyl-9-azabicyclo[3, 3, 1] non-3β-y1 α, α-di(2-thienyl) glycolate hydrochloride monohydrate (PG-501), inhibited dopamine accumulation into P
2-fraction from rat striatal homogenate in concentrations of 10
-5-10
-4 M, though atropine did not inhibit the amine accumulation even in a concentration of 10
-4 M. Furthermore, benztropine, one of the most potent inhibitors of dopamine accumulation into P
2-fraction, inhibited the accumulation into P
2V-fraction to a greater extent than that into P
2S-fraction and PG-501 inhibited the accumulation into P
2S-fraction to a greater extent than that into P
2V-fraction. The possible site of action of these two agents is discussed herein.
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