Abstract
Seven analogues of medetomidine and naphazoline were synthesized and evaluated for their alpha 1 (aorta) and alpha 2 (platelet) activities. The analogues were composed of 2- and 4-substituted imidazoles and imidazolines attached through a methylene bridge to either the 1- or 2-naphthalene ring system. In general the 1-naphthalene analogues were the most potent inhibitors of epinephrine-induced platelet aggregation. Of considerable interest was the fact that the 1-naphthalene analogues (2, 5-7) were partial agonists while the 2-naphthalene analogues (3, 8, 9) were antagonists in an alpha 1-adrenergic system (aorta). Thus, appropriately substituted naphthalene analogues of medetomidine and naphthazoline provide a spectrum of alpha 1-agonist, alpha 1-antagonist, and alpha 2-antagonist activity.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adrenergic alpha-Agonists / chemical synthesis*
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Adrenergic alpha-Agonists / pharmacology
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Adrenergic alpha-Antagonists / chemical synthesis*
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Adrenergic alpha-Antagonists / pharmacology
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Animals
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Aorta / drug effects
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Aorta / physiology
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Epinephrine / pharmacology
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Humans
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Imidazoles / chemical synthesis*
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Imidazoles / chemistry
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Imidazoles / pharmacology
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Male
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Medetomidine
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Naphazoline / analogs & derivatives
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Naphazoline / chemistry
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Naphazoline / pharmacology
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Platelet Aggregation / drug effects
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Platelet Aggregation Inhibitors / chemistry
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Platelet Aggregation Inhibitors / pharmacology
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Rats
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Vasoconstriction / drug effects
Substances
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Adrenergic alpha-Agonists
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Adrenergic alpha-Antagonists
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Imidazoles
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Platelet Aggregation Inhibitors
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4-(1-(1-naphthyl)ethyl)imidazole
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Naphazoline
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Medetomidine
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Epinephrine