In vivo studies on the effects of α1-adrenoceptor antagonists on pupil diameter and urethral tone in rabbits

Abstract

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.

Comparative effect of alfuzosin and tamsulosin on the contractile response of isolated rabbit prostatic and iris dilator smooth muscles

“…Moreover, tamsulosin's antagonistic potency in the rabbit iris dilator muscle is approximately 100 times less than its antagonistic potencies for the 3 cloned a 1 -ADR subtypes. 20 Our study does not support the conclusions of a previous investigation performed in anesthetized Japanese white rabbits, 21 showing that several a 1 -ADR antagonists, including tamsulosin and alfuzosin, inhibited PE-induced mydriasis in the same dose range as they inhibited PE-induced elevation of intraurethral pressure. However, this study in albino rabbits may not be relevant to human pharmacology.…”

Intraoperative floppy-iris syndrome associated with α1-adrenoreceptors

“…1,21 The higher risk for IFIS with tamsulosin than with alfuzosin in our study could be explained by tamsulosin's much higher specificity for the a 1A -receptor. 22 This might result in tamsulosin producing more complete and prolonged antagonism of the iris smooth muscle receptors, as Chang and Campbell 1 hypothesize.…”

The Effects of Systemic Alpha-1 Adrenergic Antagonists on Pupil Diameter in Rats

“…16 All drugs dose-dependently inhibited phenylephrineinduced pupil dilation in doses very similar to those required to produce their therapeutic effects on the lower urinary tract. Pupil diameter of rabbits that did not receive phenylephrine demonstrated that all tested alpha-1 antagonists had the potential to induce miosis, but with considerably higher doses, and such miosis is fully reversible within several hours.…”

“…Similarly, the findings of Michel et al were not compatible with any irreversible effect of alpha-1 adrenoceptor antagonists. 16 It may be argued that 1-month use of alpha-1 adrenergic antagonists might not be enough to elicit irreversible damage. However, these types of drugs usually show their clinical effect in BPH in about 24 hr, and the complaints resume shortly after the cessation of medication irrespective of the duration of the treatment period.…”