Role of alpha-2 adrenergic affinity in the action of a non-sedative antispasticity agent.
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 3H-spiperone from rat corpus striatum tissue and 3H-clonidine and 3H-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 rigidity and its potential value as an antispasticity agent may be attributed to its relatively high affinity for alpha-2 adrenergic receptors.
D000166:Acridines / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena; D002415:Cats; D005260:Female; D008297:Male; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism / Q000502:physiology*; D011954:Receptors, Dopamine / Q000378:metabolism
D000166:Acridines; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011954:Receptors, Dopamine; C031531:10-(2-dimethylaminoethyl)acridan