Abstract
Superfused vascular strips of dog dorsal metatarsal vein were used to study effects of methoxylated amphetamines and the optical isomers of 2,5-dimethoxy-4-methylamphetamine (DOM) and 2,5-dimethoxy-4-bromoamphetamine (DOB) on sympathetic nervous systems and on 5-hydroxytryptamine (5-HT) receptors. All these amphetamine derivatives produced long lasting contractions of the superfused strips. Contractions induced by para-methoxyamphetamine (PMA), 2,4-dimethoxyamphetamine (2,4-DMA), 2,5-DMA, 3,4-DMA and (+)-DOM were reduced by phentolamine (2 x 10-7 M) whereas contractions produced by (-)-DOM, (±)-, (+) and (-)-DOB were not reduced. Contractions elicited by PMA, 2,4-DMA and 3,4-DMA were antagonized by cocaine (5 x 10-6 M) but those produced by 2,5-DMA, (+)-and (-)-DOM; (±)-, (+)-and (-)-DOB were not antagonized. Responses of the vascular strips to (+)- and (-)-DOM; (±)-, (+)- and (-)-DOB were greatly antagonized by cinanserin, a 5-HT receptor antagonist. It was concluded that PMA, 2,4-DMA and 3,4-DMA produced contractions by releasing norepinephrine from sympathetic nerve terminals whereas 2,5-DMA elicited muscle contractions by directly stimulating alpha adrenergic receptors and that (+)- and (-)-DOM; (±)-, (+)- and (-)-DOB activate 5-HT receptors. PMA is the most potent in this series of compounds. The S-(+) isomers of both DOM and DOB are more potent than their corresponding R-(-) isomers in activating 5-HT receptors.
Footnotes
- Received March 26, 1973.
- Accepted September 24, 1973.
- © 1974 by The Williams & Wilkins Company
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