The enantiomers of a series of methoxy-and alkyl-substituted phenylisopropylamines were prepared by low-pressure reduction of imines formed by reaction of the appropriate phenylacetones with either (+)or (-)-a-methylbenzylamine, followed by hydrogenolysis of the hydrochlorides of the resulting-/V-(a-phenethyl)phenylisopropylamines. Values of [a]D are reported and enantiomeric purities were, in the range 96-99%. Overall yields ranged from 30 to 60%. Glc or fluorine nmr analysis of enantiomeric purity was accomplished using a-methoxy-a-trifluoromethylphenylacetamides. Glc analysis of the jV-trifluoroacetyl-S-prolylarnides was used to confirm R-(-) and S-{+) absolute configurations of all compounds. (+)or (-)-2,5-dimethoxyamphetamine was brominated to give the (+)or (-)-4-bromo compound. The enantiomers of 1,2,3,4-tetrahydro-2-naphthylamine could not be prepared by this method.Generally, optical isomers of a drug molecule possess differing degrees of biological activity. In the case of amphetamine, norepinephrine uptake into synaptosomes from noradrenergic regions of the brain is inhibited to a greater degree by the 5-(+) than by the R-(-) enantiomer.2'3 In addition, the two isomers of amphetamine are not equally good substrates for side-chain metabolizing enzymes in certain animal species.4 Since Gordis5 has found that no racemization of either isomer occurs when amphetamine is administered to man, it is possible that the complex effects of psychotomimetic amphetamines could be partially due to the fact that racemic mixtures have been used for testing.In the report by Barfknecht and Nichols® on the effects of (i?)-(-)-and (S)-(+)-3,4-dimethoxyamphetamine (3, in the rat, it was suggested that LSD could be considered as a phenethylamine derivative. Natural lysergic acid 1 possesses the 5R,8R absolute configuration7'8 and it was predicted that the psychotomimetic effects of the amphetamines might reside in the R enantiomers, based on their stereochemical relationship to lysergic acid. This prediction is consistent with stereochemical correlations between LSD, phenethylamines, and tryptamines proposed by Kang and Green.9 Indeed, it was found that the R-(-) isomer of 3,4-DMA seemed to be responsible for the psychotomimetic effects in the rat.6

Three series of bicyclic, semirigid congeners of beta-phenethylamine have been prepared for evaluation of the effect of ring size (and of concomitant conformational variation) on biological activity in a variety of assays for adrenergic and dopaminergic actions. Pharmacologic activity was associated with 2-aminotetralin and 2-aminoindan derivateves, but was not found with 6-aminobenzocycloheptene derivatives. Noteworthy is the ability of several aminotetralins and aminoindans to increase the hot-plate reaction time without eliciting dopaminergic effects. This action was not blocked by pretreatment with naloxone.

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The hypothesis of this study is that the chronic presence of intact sympathetic innervation influences the structure, and thereby function, of the rabbit ear vascular bed, and that this influence may be age related. Therefore we examined the effect of chronic sympathetic denervation on vascular resistance of the rabbit ear nine to ten weeks after unilateral superior cervical ganglionectomy. Two age groups were studied: growing juvenile rabbits denervated at 4 weeks of age and adult rabbits denervated at 16 weeks. We assessed the flow-pressure (resistance) curves of the chronically denervated and contralateral innervated isolated rabbit ears during maximum dilation. The flow-pressure curve was significantly shifted downward in the denervated compared to the contralateral innervated ears of juvenile rabbits operated on at 4 weeks (p less than 0.001) but was not different in adult rabbits operated on at 16 weeks. These results support the concept that the sympathetic nerves chronically influence blood vessel properties in growing animals, apart from their acute effect on vasomotor tone.