Structure-activity requirements for hypotension and alpha-adrenergic receptor blockade by analogues of atropine

European Journal of Pharmacology
E H CantorS Spector

Abstract

The hypotensive action of various antimuscarinic compounds structurally related to atropine was studied in conscious, unanesthetized rats. The alpha-adrenolytic activity of these agents was assessed both in vivo (blockade of norepinephrine-induced pressor response) and in vitro (displacement of [3H]WB-4101 binding). Benztropine, homatropine and hyoscyamine caused hypotension and produced alpha-adrenergic receptor blockade similar to atropine. Other analogues were either inactive (atroscine, scopolamine, tropic acid and tropine) or evoked nonspecific changes in blood pressure and lacked alpha-adrenolytic activity (benactyzine, eucatropine, methylatropine, methylhomatropine and methylscopolamine). Based on these data, we propose the following structure-activity relationship for hypotension and alpha-adrenolytic activity: (a) the tropine moiety is inactive unless it is attached to another group by an ester linkage, (b) chemical modification of the tropine moiety, including quaternization, decreases potency, (c) the d-stereoisomer appears to be more potent than the corresponding 1-form.

References

Jan 1, 1977·Blood Vessels·O A Nedergaard, J Schrold
May 1, 1974·Proceedings of the National Academy of Sciences of the United States of America·H I Yamamura, S H Snyder
Jan 1, 1974·International Review of Neurobiology·T D Inch, R W Brimblecombe
Feb 2, 1981·Life Sciences·E H CantorS Spector
Aug 22, 1980·European Journal of Pharmacology·A P CaputiH E Brezenoff
Dec 1, 1952·British Journal of Pharmacology and Chemotherapy·A FLECKENSTEIN
Sep 1, 1955·British Journal of Pharmacology and Chemotherapy·P B MARSHALL
Feb 1, 1965·British Journal of Pharmacology and Chemotherapy·W R BUCKETT, C G HAINING
Dec 1, 1948·British Journal of Pharmacology and Chemotherapy·J H BURN, N K DUTTA

Citations

Sep 13, 1989·European Journal of Pharmacology·P J Hollingsworth, C B Smith
Apr 1, 1984·Acta Physiologica Scandinavica·B LarssonA Mattiasson
Apr 28, 2007·Expert Reviews in Molecular Medicine·Ana Claudia ZenclussenHans-Dieter Volk
Feb 1, 2002·Journal of Hypertension·Rodrigo F TavaresFernando M A Corrêa

Related Concepts

Related Feeds

Adrenergic Receptors: Trafficking

Adrenergic receptor trafficking is an active physiological process where adrenergic receptors are relocated from one region of the cell to another or from one type of cell to another. Discover the latest research on adrenergic receptor trafficking here.