In vivo studies on the effects of alpha1-adrenoceptor antagonists on pupil diameter and urethral tone in rabbits.
Alpha1-adrenoceptors mediate contraction of iris dilator smooth muscle and hence pupil dilatation. We compared the ability of i.v. bolus injections of alfuzosin, doxazosin, naftopidil, prazosin, tamsulosin and terazosin to antagonise phenylephrine-induced mydriasis relative to their potency for inhibiting phenylephrine-induced elevations of intraurethral pressure (IUP) in rabbits. Moreover, we compared the ability of these drugs to induce miosis in conscious rabbits in the absence of phenylephrine. All antagonists inhibited the effects of phenylephrine on pupil size and IUP, and the ratio of the respective ED50 values was close to unity in all cases. The doses required to induce statistically significant miosis in the absence of phenylephrine were 30- to 100-fold higher than those inhibiting phenylephrine-induced mydriasis for all antagonists, except for naftopidil. Moreover, the miotic effects of all alpha1-adrenoceptor antagonists were fully reversible within 8 h. We conclude that alfuzosin, doxazosin, naftopidil, prazosin, tamsulosin and terazosin inhibit phenylephrine-induced mydriasis in the same dose range as they inhibit elevations in IUP. Higher doses of all antagonists are required to induce miosis in the absence of an exogenous agonist, and such miosis is always reversible within hours.
Michel
Martin C
MC
Department of Pharmacology and Pharmacotherapy, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. m.c.michel@amc.uva.nl
Okutsu
Hiroko
H
Noguchi
Yukiko
Y
Suzuki
Masanori
M
Ohtake
Akiyoshi
A
Yuyama
Hironori
H
Yanai-Inamura
Hiroko
H
Ukai
Masashi
M
Watanabe
Mai
M
Someya
Akiyoshi
A
Sasamata
Masao
M
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D017292:Doxazosin / Q000494:pharmacology; D008297:Male; D011224:Prazosin / Q000031:analogs & derivatives / Q000494:pharmacology; D011680:Pupil / Q000187:drug effects* / Q000502:physiology; D011799:Quinazolines / Q000494:pharmacology; D011817:Rabbits; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D013997:Time Factors; D014521:Urethra / Q000187:drug effects* / Q000502:physiology
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D011799:Quinazolines; D018340:Receptors, Adrenergic, alpha-1; C041226:Terazosin; C047638:alfuzosin; D017292:Doxazosin; D011224:Prazosin