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Role of alpha‐2 adrenergic affinity in the action of a non‐sedative antispasticity agent
Author(s) -
Anderson R. J.,
Brigham P.,
Cady W. J.,
Kellar K. J.
Publication year - 1982
Publication title -
acta neurologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.967
H-Index - 95
eISSN - 1600-0404
pISSN - 0001-6314
DOI - 10.1111/j.1600-0404.1982.tb04522.x
Subject(s) - reserpine , endocrinology , medicine , clonidine , alpha 2 adrenergic receptor , chemistry , agonist , dopamine receptor , pharmacology , adrenergic receptor , dopamine , receptor , muscarinic acetylcholine receptor , alpha 1a adrenergic receptor , adrenergic , beta 3 adrenergic receptor
Muscle hypertonus of central origin can be effectively reversed by either dopamine agonists or alpha‐adrenergic antagonists. Because of its efficacy in reversing reserpine rigidity (a syndrome resembling Parkinsonism), SKF‐7265 was examined to determine whether its action was mediated through alpha‐adrenergic or dopaminergic receptors. The pharmacologic blocking activity of SKF‐7265 was assessed by measuring blockade of the cardiovascular agonist responses induced by norepinephrine, epinephrine, isoproterenol, acetylcholine and histamine. The binding affinity of SKF‐7265 was determined by displacement of 3 H‐spiperone from rat corpus striatum tissue and 3 H‐clonidine and 3 H‐WB‐4101 displacement from rat cerebral cortical tissue. Using the cardiovascular responses, SKF‐7265 was devoid of beta‐adrenergic or cholinergic blocking effects and did not produce any behavioral or reflex deficits in awake animals. Receptor binding studies showed that SKF‐7265 had equal affinity for alpha‐1 and alpha‐2 adrenergic receptors and little affinity for dopamine receptors. It is concluded that the efficacy which has been reported for the SKF‐7265 induced reversal of reserpine rigdity and its potential value as an antispasticity agent may be attributed to its relatively high affinity for alpha‐2 adrenergic receptors.