- A study of the conformational requirements for direct adrenergic stimulation
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A group of tetrahydroisoquinoline derivatives was prepared as fixed cisoid and 2 indanamines as fixed transoid analogs of the adrenergic neurotransmitter, norepinephrine. The compounds were evaluated in comparison with their closest, flexible counterparts, epinine and (R) and (S) α methyldopamine, respectively, for direct α and β adrenergic activities in vivo and in vitro. Results obtained in vivo on the cat nictitating membrane indicate that a transoid conformation is better than cisoid for inducing direct α stimulation but that a cisoid conformation does not preclude direct α activity. No conclusion could be reached with regard to conformational requirements for direct β activity.
- Gray,Reit,Ackerly,Hava
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- Conformationally Restricted Congeners of Dopamine Derived from 2-Aminoindan
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Two series of N-substituted 2-aminoindan systems have been prepared: 4,5-dihydroxy-2-aminoindan (1) has a hydroxylation pattern analogous to the α-conformer of dopamine, and 5,6-dihydroxy-2-aminoindan (2) has a hydroxylation pattern of the β conformer of dopamine.All members of both series demonstrated only extremely weak binding to calf caudate homogenate.Certain N-alkylated 4,5-dihydroxyindans were violent emetics in the dog and were potent in blockade of the effect of stimulation of the cardioaccelerator nerve of the cat.In contrast, the 5,6-dihydroxy series displayed low or no activity/potency in these assays.Conformational analysis of the 2-aminoindan system is described and discussed.
- Cannon, Joseph G.,Perez, Julio A.,Bhatnagar, Rambir K.,Long, John Paul,Sharabi, Fouad M.
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p. 1442 - 1446
(2007/10/02)
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