A Difference in Mode of Antagonism between Optical Isomers of a Potent Selective Alphai-Adrenoceptor Blocker (YM-12617) and Norepinephrine in Isolated Rabbit Iris Dilator and Aorta

Takayanagi, Issei; Konno, Fukio; Kameda, Hiroyuki; Kubo, Haruichi; Furukawa, Akira; Toyoda, Toshie

doi:10.1254/jjp.42.579

Cited by 13 publications

(3 citation statements)

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“…The difference in receptor pharmacology between pigmented and albino rabbits is further supported by our data showing that tamsulosin potency in iris dilator smooth muscle from pigmented rabbits (pA 2 Z 7.96) was much lower than that previously observed in albino rabbits (pA 2 Z 9.73), 22 confirming results obtained with 5-methylurapidil. 13 On the basis of these comparisons, we conclude that the a 1 -ADR pharmacology of the human iris appears to more closely resemble that of the pigmented rabbit iris than the albino rabbit iris.…”

Section: Discussionsupporting

confidence: 89%

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

Palea

Chang

Rekik

et al. 2008

Journal of Cataract and Refractive Surgery

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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.

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Section: Discussionsupporting

confidence: 89%

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

Palea

Chang

Rekik

et al. 2008

Journal of Cataract and Refractive Surgery

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“…The pD2 values varied from 6.04 to 8.36 (Table 1). The concentration-response curves of norepi nephrine were shifted to the right in a par allel manner by a 10-min treatment with the al-adrenoceptor competitive antagonist YM 12617 (15,16) at concentrations of 10-9, 3 X 10-9 and 10-8 M in all strips. Schild plots of these results yielded straight lines with a slope of 1.…”

Section: Resultsmentioning

confidence: 89%

Variation in Sensitivity of .ALPHA.1-Adrenoceptor Stimulants and .ALPHA.1-Adrenoceptor Mechanisms in Rabbit Arteries.

1991

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Sensitivity (pD2 value, negative logarithm of the molar concentration producing the half maximum response) and affinity (pKA value, negative logarithm of dissociation constant) of norepinephrine were determined in 6 arteries from rabbits. A positive correlation was found in the pD2 and pKA values of norepinephrine. The slope was not significantly different from 1. The pD2 and pKP (a negative logarithm of dissociation constant of a partial agonist) values of tizanidine, an a,-partial agonist, were also determined. There were positive correlations between the pD2 and pKP values of tizanidine and also between the two pD2 values of norepinephrine and tiza nidine. The slopes were not significantly different from 1. These results suggest that the regional differences in pD2 values of norepinephrine and tizanidine in the arteries are partly due to the affinity and suggest that both drugs interact with one recognition site in the al-adrenoceptors. The dissociation constants, KD values, and the maximum binding sites, Bmax, for [125I]-HEAT were also estimated by Scatchard analysis of the specific binding of [125I]-HEAT to the membrane fractions from rabbit arteries. The KD values for [125I]-HEAT were also identical. However, Bmax varied considerably among rabbit arteries. There was a positive correlation between the logarithm of Bmax and the pD2 values for norepinephrine. The present results suggest that the regional difference in the pD2 values for norepinephrine in rabbit arteries is due to variations in the affinities to the al-adrenoceptors as well as the receptor densities.Remarkable differences have been detected in the sensitivity of isolated vascular smooth muscles to norepinephrine. Some of these dif ferences may be at least partly related to the difference in subtypes of a1-adrenoceptors. Recently, a regional difference in the nor epinephrine sensitivity, the pD2 value (a nega tive logarithm of a molar concentration pro ducing a half maximum response), of the drugs was reported in both arteries and veins. The affinity of norepinephrine to the a1-adre noceptors, the pKA values (the negative loga rithm of dissociation constant), was the pri mary determinant of sensitivity (pD2 values) to these drugs in the arteries from rabbits (1 3) and dogs (4). In contrast, the regional dif ference in sensitivity (pD2 value) for norepi nephrine in canine veins was related to the total concentration of the al-adrenoceptors or receptor density, but not to the affinity (pKA value) of norepinephrine to the a1-adre noceptors (5). Therefore, Takayanagi et al. (4) concluded that there is a qualitative differ ence between the al-adrenoceptor mechanisms

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“…An animal study has shown one form to be 140 times more potent in the prostate than the other [33] . The more potent form is an irreversible antagonist of norepinephrine in human isolated prostate [34] and the iris dilator muscle as shown in an experimental animal study [35] . However, in another study, it has been advocated that the blocking effect of tamsulosin on the α-1 receptors on iris tissue can be prevented by binding these receptors with the natural agonist epinephrine.…”

Section: Discussionmentioning

confidence: 92%

Is sulfonamide group of tamsulosin main factor in the pathophysiology of floppy iris syndrome?

Ürkmez¹

2018

Haydarpasa Numune Med J

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Intraoperative floppy iris syndrome (IFIS) was first described by Chang et al. in 2005 in using α-blockers. Tamsulosin a selective α-(a) adrenergic receptor (AR) antagonist is a commonly prescribed drug for benign hyperplasia of the prostate (BPH), and it has been shown to have the strongest association with IFIS. Other drugs that predispose to IFIS include alfuzosin, doxazosin, terazosin, finasteride, labetalol, mianserin, chlorpromazine, donepezil and other antipsychotic agents. In literature reviews, the pathophysiological evaluation of IFIS has not yielded clear results. In the present study, we examined this pathophysiological mechanism from a different perspective and somewhat hypothetically analyzed the chemical composition of these drugs. We analyzed their chemical formulas and pharmacological effects in combination. We compared tamsulosin with other IFIS-inducing α-blockers and propose that its sulfonamide group might be a causative factor.

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A Difference in Mode of Antagonism between Optical Isomers of a Potent Selective Alphai-Adrenoceptor Blocker (YM-12617) and Norepinephrine in Isolated Rabbit Iris Dilator and Aorta

Abstract: Optical isomers of YM-1 2617, a potent and selective alpha, -adrenoceptor blocker, were tested on the rabbit iris dilator and aorta. The order of potency was R(-) isomer>racemate>S(+)-isomer.

Cited by 13 publications

References 5 publications

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

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

Variation in Sensitivity of .ALPHA.1-Adrenoceptor Stimulants and .ALPHA.1-Adrenoceptor Mechanisms in Rabbit Arteries.

Is sulfonamide group of tamsulosin main factor in the pathophysiology of floppy iris syndrome?

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