Abstract
COYLE and Snyder1 reported that various antiparkinson drugs inhibit the uptake of labelled dopamine (DA) into striatal synaptosomes. They suggested that these drugs may act in part by a potentiation of dopaminergic neurotransmission caused by inhibition of DA uptake. Measurement of drug effects on the uptake of labelled DA into slices or synaptosomes from the corpus striatum has become a widely used test for the evaluation of drugs affecting central dopaminergic functions. Some observations made in our laboratory, however, suggest that the apparent reduction of 3H-DA uptake caused by a variety of drugs in in vitro experiments may, in fact, be the result of a DA-depleting action. Benztropine and nomifensine are said to be potent DA-uptake inhibitors2; however, in our experience, benztropine (30 mg kg−1 subcutaneously) does not inhibit, and nomifensine (100 mg kg−1 orally) only slightly inhibits, the uptake of 3H-DA into striatal synaptosomes prepared from rats pretreated 1 h before killing. In contrast, pretreatment with tricyclic antidepressants does inhibit NA and 5-hydroxytryptamine (5-HT) uptake into midbrain synaptosomes3. Using the method of Farnebo4, we studied the effects of benztropine, haloperidol, chlorpromazine, d-amphetamine, piroheptine5 and cocaine on the release of tritium from field-stimulated, 3H-DA-prelabelled striatal slices. We observed that, at concentrations between 10−6M and 10−5M, these drugs increase the spontaneous release of tritium soon after their addition to the superfusion medium.
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References
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BAUMANN, P., MAITRE, L. Is drug inhibition of dopamine uptake a misinterpretation of in vitro experiments?. Nature 264, 789–790 (1976). https://doi.org/10.1038/264789a0
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DOI: https://doi.org/10.1038/264789a0
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