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In general, __-adrenergic receptors mediate contraction and hypertrophic growth of smooth muscle cells. __-Receptors are 7-transmembrane domain receptors coupled to G proteins, Gq/__. Three __-receptor subtypes, which share approximately 75% homology in their transmembrane domains, have been identified: __A (chromosome 8), __B (chromosome 5), and __D (chromosome _0). Terazosin is the first __-receptor antagonist to demonstrate selectivity for the __A-receptor. All three receptor subtypes appear to be involved in maintaining vascular tone. The __A-receptor maintains basal vascular tone while the __B-receptor mediates the vasocontrictory effects of exogenous __-agonists. Activation of __-receptors activates Gq-proteins, which results in intracellular stimulation of phospholipases C, A_, and D. This results in mobilization of Ca_+ from intracellular stores, activation of mitogen-activated kinase and PI_ kinase pathways and subsequent vasoconstriction. Terozosin produces its pharmacological effects by inhibiting __A-receptor activation. Inhibition of these receptors in the vasculature and prostate results in muscle relaxation, decreased blood pressure and improved urinary outflow in symptomatic benign prostatic hyperplasia.
Terazosin, classified as a quinazoline, is similar to doxazosin and prazosin. As an _-adrenergic blocking agent, terazosin is used to treat hypertension and BPH. Terazosin produces vasodilation and reduces peripheral resistance but in general has only a slight effect on cardiac output. The antihypertensive effect with chronic dosing is not usually accompanied by reflex tachycardia.
Hepatic. One of the four metabolites identified (piperazine derivative of terazosin) has antihypertensive activity.
LD50=259.3mg/kg (IV in mice)
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