The EFFECTS OF AMOSULALOL, a NOVEL COMBINED Α‐ AND Β‐ADRENORECEPTOR ANTAGONIST, ON THE RAT ISOLATED RIGHT VENTRICLE AND AORTA

Hughes, Enid L.; Doggrell, Sheila A

doi:10.1111/j.1474-8673.1985.tb00117.x

Cited by 6 publications

(2 citation statements)

References 14 publications

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“…Previous studies have demonstrated that non-cumulative 5-HT addition to the rat aorta produces initial fast and secondary slow contractile responses (Hughes & Doggrell, 1985;Nakaki, Roth, Chuang & Costa, 1985;Doggrell, 1987). The present study demonstrates that immediate fast and secondary slow responses of the rat aorta are also obtained on cumulative 5-HT addition.…”

Section: Discussionmentioning

confidence: 98%

Further analysis of the inhibitory effects of dihydroergotamine, cyproheptadine and ketanserin on the responses of the rat aorta to 5‐hydroxytryptamine

Doggrell

1992

Journal of Autonomic Pharmacology

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1. The aim of the present study was to analyse the inhibitory effects of dihydroergotamine, cyproheptadine and ketanserin on the rat aorta contractile responses to 5-HT. Initially phenoxybenzamine treatment was used to determine whether spare receptors exist at the maximum responses to 5-HT. Then the reversibility of the inhibitory effects of phentolamine, dihydroergotamine, cyproheptadine and ketanserin against the fast and slow response of the rat aorta to 5-HT were determined. 2. Phenoxybenzamine caused non-parallel rightward shifts of the 5-HT concentration-response curves with reduced maximal responses. The KA values for 5-HT to produce fast and slow responses were 2-5 x 10(-5) M. These KA values are much higher than those previously reported for 5-HT at 5-HT2-receptors and suggest that the 5-HT2-receptor of the rat aorta is 'atypical'. The rat aorta has spare 5-HT-receptors for the maximal fast and slow responses to 5-HT. 3. Phentolamine, dihydroergotamine, cyproheptadine and ketanserin inhibited the fast and slow responses to 5-HT. Phentolamine and ketanserin and the higher concentrations of dihydroergotamine and cyproheptadine tested had greater inhibitory effects on the fast than slow 5-HT responses possibly because the fast 5-HT response did not always reach equilibrium in the presence of antagonists. 4. The inhibitory effects on 5-HT responses of phentolamine at 10(-6)-10(-5) M were readily reversible, those of cyproheptadine at 10(-9)-10(-8) M and ketanserin at 10(-8) M were slowly reversible and those of dihydroergotamine at 10(-9)-10(-8) M were irreversible by washing in drug-free Krebs. 5. The inhibitory effects of phentolamine and ketanserin were not altered by increasing the treatment time whereas some of the effects of cyproheptadine and the effects of dihydroergotamine on responses to 5-HT were increased by prolonging the contact time with the antagonist from 75 to 150 min. 6. The present study shows that at the rat aorta 5-HT2-receptor, phentolamine is a competitive readily reversible, cyproheptadine and ketanserin are competitive slowly reversible and dihydroergotamine is a competitive irreversible antagonist.

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Section: Discussionmentioning

confidence: 98%

Further analysis of the inhibitory effects of dihydroergotamine, cyproheptadine and ketanserin on the responses of the rat aorta to 5‐hydroxytryptamine

Doggrell

1992

Journal of Autonomic Pharmacology

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“…It was not unexpected that ( f )-, ( + )-, and (-)-amosulalol caused membrane stabilizing activity on the rat left atria as we have previously demonstrated membrane stabilizing activity with these drugs on the rat right ventricle. 11,14 The mechanism underlying membrane stabilizing activity with P-blockers on the heart is poorly defined. The concentration of ( f )-amosulalol and ( f )-propranolol that causes membrane-stabilizing activity is dependent on the cardiac tissue studied.…”

Section: Discussionmentioning

confidence: 99%

The effects of (±)‐, (+)‐, and (−)‐atenolol, sotalol, and amosulalol on the rat left atria and portal vein

Doggrell

1993

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The effects of (+/-)-, (+)-, and (-)-atenolol, sotalol, and amosulalol alone on the rat left atria and portal vein and on the respective beta 1- and beta 2-adrenoceptor-mediated responses to isoprenaline have been determined. (+/-)-Atenolol at 10(-6) M had no effect whereas high concentrations of (+/-)- and (-)-sotalol, 10(-5)-10(-4) M, and (+/-)-, and (-)-amosulalol depressed the response of the rat left atria to cardiac stimulation which indicates membrane stabilizing activity. None of the drugs tested had any effect alone on the rat portal vein. The order of potency as antagonists was (+/-)-amosulalol > (+/-)-atenolol > (+/-)-sotalol at beta 1-adrenoceptors and (+/-)-amosulalol > (+/-)-sotalol > (+/-)-atenolol at beta 2-adrenoceptors. (+/-)-Atenolol and (+/-)-amosulalol are beta 1-selective whereas (+/-)-sotalol is beta 2-selective. For each of the racemic beta-blockers, the beta 1- and beta 2-adrenoceptor blocking activity was predominantly due to the (-)-enantiomer.

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Comparison of the Effects of Labetalol and SCH 19927, the Rir Isomer of Labetalol, on the Rat Isolated Right Ventricle and Aorta

Doggrell¹,

Hughes²

1985

Journal of Autonomic Pharmacology

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The effects of labetalol and its R1R isomer, SCH 19927, on the accumulation of radioactivity from [3H]-noradrenaline, and on the subsequent spontaneous and nerve-evoked outflow of radioactivity have been investigated in the rat isolated right ventricle. In addition, the effect of these agents on the contractions of the electrically-driven rat right ventricle to isoprenaline and of the rat isolated aorta to phenylephrine and 5-hydroxytryptamine are reported. Labetalol and SCH 19927 (both at 10(-6)M) inhibited the accumulation of radioactivity from [3H]-noradrenaline by 26 and 37%, respectively. The spontaneous outflow of radioactivity, following loading of the ventricle with [3H]-noradrenaline, was increased by labetalol and SCH 19927 (both at 10(-6)M) by a cocaine and idazoxan-insensitive mechanism. The nerve-evoked outflow of radioactivity was increased by labetalol and SCH 19927 (both at 10(-6)M). The ability of labetalol and SCH 19927, to increase nerve-evoked outflow was maintained in the presence of cocaine (10(-5)M) or idazoxan (10(-7)M) but reversed in the presence of cocaine and idazoxan. It is suggested that labetalol and its R1R isomer act both to inhibit neuronal uptake of noradrenaline and as antagonists at prejunctional alpha 2-adrenoreceptors. Labetalol and SCH 19927 reduced the contractile responses associated with the nerve-evoked outflow of radioactivity probably mainly by acting as antagonists at postjunctional beta 1-adrenoreceptors. The contractile responses of the electrically-driven rat right ventricle to isoprenaline were inhibited by labetalol and SCH 19927. SCH 12297 (pA2 = 8.9) was 4 times more potent than labetalol (pA2 = 8.3) as a beta 1-adrenoreceptor antagonist. The ability of labetalol and SCH 19927 at greater than or equal to 10(-7)M to depress maximal responses to isoprenaline may represent membrane stabilizing activity. The contractile responses of rat aorta to phenylephrine were inhibited by labetalol and SCH 19927. Labetalol (pA2 = 7.5) was 4X more potent than SCH 19927 (pA2 = 6.9) as an alpha 1-adrenoreceptor antagonist. SCH 19927 and labetalol had no effect on contractile responses to 5-hydroxytryptamine.

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The EFFECTS OF AMOSULALOL, a NOVEL COMBINED Α‐ AND Β‐ADRENORECEPTOR ANTAGONIST, ON THE RAT ISOLATED RIGHT VENTRICLE AND AORTA

Cited by 6 publications

References 14 publications

Further analysis of the inhibitory effects of dihydroergotamine, cyproheptadine and ketanserin on the responses of the rat aorta to 5‐hydroxytryptamine

Further analysis of the inhibitory effects of dihydroergotamine, cyproheptadine and ketanserin on the responses of the rat aorta to 5‐hydroxytryptamine

The effects of (±)‐, (+)‐, and (−)‐atenolol, sotalol, and amosulalol on the rat left atria and portal vein

Comparison of the Effects of Labetalol and SCH 19927, the Rir Isomer of Labetalol, on the Rat Isolated Right Ventricle and Aorta

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