Effects of rigid amphetamine analogs on vascular strips: studies of 2-aminotetrahydronaphthalene and 2-aminoindan derivatives.
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The hallucinogenic drugs represent a recurrent outbreak pattern with each generation or two seeming to rediscover their ego-dissolving effects. The inhalants produce a short-lived intoxication with certain volatile solvents affecting specific organ systems.
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Rats trained to discriminate (+/-) 2,5-dimethoxy-4-methylphenylisopropylamine (DOM) (1.0 mg/kg) from saline, using a standard two-lever operant task, were challenged with various doses of 3,4-methylenedioxyphenylisopropylamine (MDA) and several related agents. The (+/-)-DOM stimulus generalized to (+/-)-MDA, suggesting that both agents apparently produce similar stimulus cues. Related agents, known to produce effects in man similar to those produced by (+/-)-MDA, also resulted in generalization when administered to the DOM-trained animals, e.g., R(-)-MDA and a methoxylated derivative of (+/-)-MDA, (+/-)-2-OMe-4,5-MDA. DOM stimulus generalization was not observed for S(+)-MDA, the N-monomethyl and alpha-demethyl derivatives of MDA, nor for a metabolite of MDA (i.e., 3-methoxy-4-hydroxyphenylisopropylamine). The results suggest that R(-)- and (+/-)-MDA, as well as (+/-)-2-OMe-4,5-MDA, but not the other derivatives of MDA, are capable of producing behavioral (stimulus) effects common to those produced by the training dose of (+/-)-DOM.
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Attempts have been made to correlate hyperthermic potencies in rabbits and LSD-like effect in rat of a series of phenylisopropylamines (amphetamines) with physico-chemical parameters. In case of 2,4,5-trisubstituted analogs, hyperthermic potencies are found to be well correlated parabolically with the hydrophobic parameter pi. However, for the same series, the LSD-like effect is found to be related with pi in combination of steric parameter of 4-substituent. It is therefore inferred that hyperthermia in rabbit may be the function only of the hydrophobic character of molecule, but the LSD-like effect is influenced by the steric hindrance of 4-substituent also.
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