Abstract
The dopamine-releasing actions of neumoleptics and of ethanol were studied on rat caudate synaptosome fractions (unpurified) which had been loaded with 3H-dopamine in vitro. The threshold concentrations above which the neuroleptics enhanced the spontaneous release of dopamine from the synaptosomes were 3.5 x l0-6 M for chlorpromazine, 10-7 M for haloperidol, 3.5 x 10-9 M for reserpine phosphate, 10-7 M for pimozide and 3 x l0-6 M for benztropine. The threshold concentrations above which the uptake of dopamine was inhibited were genenally about 5 to 10 times higher. The threshold concentration above which ethanol potentiated the spontaneous release of dopamine from the synaptosome fraction was 0.05 M or 0.23 g/100 ml. This concentration produces general anesthesia in the human. It is postulated that the side effects of neuroleptic-induced parkinsonism and tardive dyskinesia are based on the impulse-blocking and dopamine-releasing actions of the neuroleptics, respectively.
Footnotes
- Received July 26, 1973.
- Accepted February 7, 1974.
- © 1974 by The Williams & Wilkins Company
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|