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Abstract

Differential inhibition of beta adrenergic receptors in human and rabbit ciliary process and heart.

J A Nathanson
Journal of Pharmacology and Experimental Therapeutics January 1985, 232 (1) 119-126;
J A Nathanson
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Abstract

Prior biochemical studies have suggested that beta adrenergic receptors in the ciliary process are mostly of the beta-2 subtype. The present experiments evaluate a number of beta adrenergic antagonists, including several recently developed drugs, for their ability to block rabbit and human ciliary process and heart beta adrenergic receptors activating adenylate cyclase. Three of these agents (alpha-methylpropranolol, IPS 339 and ICI 118,551) demonstrated a high degree of oculoselectivity in both rabbit and human. The other agents (S 37-429, S 32-468, ICI 78,462,H35/25, butoxamine, propranolol, timolol, atenolol and practolol) showed either modest or no oculoselectivity. Structure-activity studies suggested that, among antagonists of the aryloxymethyl type, methylation of the side-chain alpha-carbon or the aromatic ring may enhance oculoselectivity primarily by decreasing potency at cardiac beta adrenergic receptors. Additional physiological studies of cardiac chronotropic response revealed that, compared with nonselective beta blockers, compounds with biochemical oculoselectivity demonstrate decreased physiological effects on cardiac function. This was true when the selective agents were applied either systemically or topically to the eye. On the other hand, the systemic absorption of topical timolol was sufficient to block cardiac chronotropic effects completely. These findings, identifying relatively specific blockers of rabbit and human ciliary process beta adrenergic receptors, have implications for the development of ocular hypotensive agents with fewer systemic side effects on tissues enriched in beta-1 adrenergic receptors.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 232, Issue 1
1 Jan 1985
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Abstract

Differential inhibition of beta adrenergic receptors in human and rabbit ciliary process and heart.

J A Nathanson
Journal of Pharmacology and Experimental Therapeutics January 1, 1985, 232 (1) 119-126;

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Abstract

Differential inhibition of beta adrenergic receptors in human and rabbit ciliary process and heart.

J A Nathanson
Journal of Pharmacology and Experimental Therapeutics January 1, 1985, 232 (1) 119-126;
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