Comparative effect of alfuzosin and tamsulosin on the contractile response of isolated rabbit prostatic and iris dilator smooth muscles: possible model for intraoperative floppy-iris syndrome.
OBJECTIVE
To compare the pharmacologic properties of tamsulosin and alfuzosin in isolated prostatic and iris dilator smooth muscle from pigmented rabbits.


METHODS
UROsphere Laboratories, Université Paul Sabatier, Toulouse, France.


METHODS
Prostatic and iris dilator smooth muscle strips were placed in organ baths. A concentration-response curve to phenylephrine was compared before and after incubation with tamsulosin or alfuzosin.


RESULTS
Both drugs were approximately 30 times less potent in iris dilator than prostatic smooth muscle. In the iris, tamsulosin acted as a competitive antagonist starting at the 0.03 microM concentration (pA(2)=7.96). This is in the same range as the maximum plasma concentration after a 0.4 mg dose of tamsulosin in humans (0.025 microM). The antagonistic effect of alfuzosin in the iris was weaker (calculated mean pA(2) value of 5.63+/-0.19). Concentrations with an equipotent antagonistic effect on rabbit iris dilator muscle (3.0 and 10.0 microM) were approximately 100 to 300 times higher than the maximum plasma concentrations after a 10.0 mg dose of alfuzosin in humans (0.032 microM).


CONCLUSIONS
Tamsulosin was more effective than alfuzosin at blocking adrenergic contraction of the iris dilator muscle in pigmented rabbits. Both drugs were less potent in the iris than in the prostate, which suggests that an additional iris receptor could be involved. If valid in humans, our results suggest that attainable plasma concentrations of tamsulosin are able to antagonize iris dilator smooth muscle contraction, whereas those of alfuzosin are not. This could explain the higher frequency of intraoperative floppy-iris syndrome in patients treated with tamsulosin than with alfuzosin.
Palea
Stefano
S
UROsphere, Faculté des Sciences Pharmaceutiques, Ecole Nationale Vétérinaire de Toulouse, Toulouse, France.
Chang
David F
DF
Rekik
Moez
M
Regnier
Alain
A
Lluel
Philippe
P
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007431:Intraoperative Complications; D007498:Iris / Q000187:drug effects*; D007499:Iris Diseases / Q000473:pathology*; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects*; D011799:Quinazolines / Q000494:pharmacology*; D011817:Rabbits; D013449:Sulfonamides / Q000494:pharmacology*; D013566:Sympathomimetics / Q000494:pharmacology; D013577:Syndrome; D000077409:Tamsulosin
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D011799:Quinazolines; D013449:Sulfonamides; D013566:Sympathomimetics; D010656:Phenylephrine; C047638:alfuzosin; D000077409:Tamsulosin