PT - JOURNAL ARTICLE AU - Reinhard Sarges AU - B. Kenneth Koe AU - Albert Weissman AU - John P. Schaefer TI - BLOCKADE OF HEART <sup>3</sup>H-NOREPINEPHRINE UPTAKE BY 4-PHENYL-1-AMINOTETRALINES: IMPLICATIONS FOR THE ACTIVE CONFORMATION OF IMIPRAMINE-LIKE DRUGS DP - 1974 Dec 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 393--402 VI - 191 IP - 3 4099 - http://jpet.aspetjournals.org/content/191/3/393.short 4100 - http://jpet.aspetjournals.org/content/191/3/393.full SO - J Pharmacol Exp Ther1974 Dec 01; 191 AB - A series of phenyl substituted 1-aminotetraline (1-amino-1,2,3,4-tetrahydronapththalene) derivatives was examined for effects on uptake of exogenous 3H-norepinephrine into rat heart and on reserpine-induced hypothermia in mice. trans-4-Phenyl derivatives with small nitrogen substituents were found to block norepinephrine uptake and to reverse reserpine-induced hypothermia with consistently greater effectiveness than their often inactive cis isomers. 1R,4S-N-methyl-4-phenyl-1,2,3,4-tetrahydro-1-naphthylamine (1aα) was the most potent uptake blocker of this series. Its enantiomer was inactive, indicating the existence of a stereospecific receptor at the norepinephrine uptake pump. The structural and functional resemblance of this compound to desipramine suggests that in the active conformation the aminoalkyl side chain of tricyclic antidepressants is folded toward the aromatic ring. This hypothesis is supported by the potent uptake blockade observed with the nontricyclic agent, EXP-561 (1-amino-4-phenylbicyclo[2.2.2]octane), and by the relative inactivity of cyproheptadine [4-(5H-dibenz-[a,d]cyclohepten-5-ylidine)-1-methylpiperidine]. © 1974 by The Williams &amp; Wilkins Co.