It is used in the treatment ofhypertension, and specifically that caused bypheochromocytoma. It has a slower onset and a longer-lasting effect compared with other alpha blockers.
It was also the firstalpha blocker to be used for treatment ofbenign prostatic hyperplasia,[2] although it is currently seldom used for that indication due to unfavourable side effects.
It is also used incomplex regional pain syndrome (CRPS) type 1 due to itsantiadrenergic effects. It has shown to be beneficial if used in the first 3 months of the CRPS diagnosis.
Phenoxybenzamine has long been known to blockejaculation without affecting semen quality or ability to achieve orgasm, which could make it an effective male contraceptive. This effect is completely reversible, and is believed to be the result of alpha-1 adrenoceptor blockade in the longitudinal muscles of thevas deferens.[4][5][6] A dose of 20 mg/day results inaspermia due to reversible paralyzing effects on the vas deferens, ampulla, and ejaculatory ducts.[7] Due to these actions, phenoxybenzamine is also useful for the treatment ofpremature ejaculation in men.[7]
Phenoxybenzamine is used as an anti-hypertensive due to its efficacy in reducing thevasoconstriction caused byepinephrine (adrenaline) andnorepinephrine. Phenoxybenzamine forms a permanent covalent bond withadrenergic receptors. Based on known information about the structures of these receptors, it likely involves attack by the cysteine at position 3.36 in transmembrane helix 3 to form a stable linkage.[8] Thus, it remains permanently bound to the receptor, preventing adrenaline and noradrenaline from binding. This causes vasodilation in blood vessels, due to itsantagonistic effect at the alpha-1 adrenoceptor found in the walls of blood vessels, resulting in a drop in blood pressure. A side effect of phenoxybenzamine is reflextachycardia.
As a non-selective alpha receptor antagonist, it will also affect both the postsynaptic alpha-1 and presynaptic alpha-2 receptors in the nervous system, and so reducesympathetic activity. This results in further vasodilation, pupil constriction, an increase inGI tract motility and secretions, andglycogen synthesis.
Clinically, non-selective alpha antagonists block alpha receptors (but do not differentiate between alpha-1 and alpha-2). They are used as antihypertensives because they block alpha-receptor-mediated vasoconstriction. The block on alpha-2 receptors further potentiates beta-effects, increasing cardiac output.
Phenoxybenzamine has a long-lasting action, binding covalently to the alpha receptors. Its only current clinical use is in preparing patients withpheochromocytoma for surgery; its irreversible antagonism and the resultant depression in the maximum of the agonist dose-response curve are desirable in a situation where surgical manipulation of the tumour may release a large bolus of pressor amine into the circulation. Typically, phenoxybenzamine is not used in the long term, as new receptors are made to upregulate alpha stimulation. The main limiting side-effects of alpha antagonists is that the baroreceptor reflex is disrupted and thus this can cause postural hypotension.
Phenoxybenzamine contains a stereocenter, so there are twoenantiomers, the (R)- and the (S)-forms. All commercial preparations contain the drug asracemate.[13]
^Caine M, Perlberg S, Meretyk S (December 1978). "A placebo-controlled double-blind study of the effect of phenoxybenzamine in benign prostatic obstruction".British Journal of Urology.50 (7):551–554.doi:10.1111/j.1464-410X.1978.tb06210.x.PMID88984.
^Kjaergaard N, Kjaergaard B, Lauritsen JG (June 1988). "Prazosin, an adrenergic blocking agent inadequate as male contraceptive pill".Contraception.37 (6):621–629.doi:10.1016/0010-7824(88)90008-X.PMID2899490.
^Homonnai ZT, Shilon M, Paz GF (May 1984). "Phenoxybenzamine--an effective male contraceptive pill".Contraception.29 (5):479–491.doi:10.1016/0010-7824(84)90022-2.PMID6430643.
^Doggrell SA (October 1995). "Increase in affinity and loss of 5-hydroxytryptamine2A-receptor reserve for 5-hydroxytryptamine on the aorta of spontaneously hypertensive rats".Journal of Autonomic Pharmacology.15 (5):371–377.doi:10.1111/j.1474-8673.1995.tb00403.x.PMID8744977.
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