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. 1972 Aug;45(4):660–675. doi: 10.1111/j.1476-5381.1972.tb08125.x

Pharmacology of AH 5158; a drug which blocks both α- and β-adrenoceptors

J B Farmer, I Kennedy, G P Levy, R J Marshall
PMCID: PMC1665961  PMID: 4404413

Abstract

1. AH 5158 differs from conventional adrenoceptor blocking drugs in producing competitive blockade of both α- and β-adrenoceptors.

2. AH 5158 is 5-18 times less potent than propranolol in blocking β-adrenoceptors. It resembles propranolol in its non-selective blockade of β1-cardiac and β2-vascular and tracheal adrenoceptors and in its lack of intrinsic sympathomimetic activity.

3. AH 5158 is 2-7 times less potent than phentolamine in blocking α-adrenoceptors. AH 5158 itself is more active on β- than α-adrenoceptors.

4. Blockade of noradrenaline vasopressor responses by AH 5158 in anaesthetized dogs was dose-dependent up to 1 mg/kg but no further blockade was obtained with larger doses of AH 5158. `Self-limiting' blockade was not observed in dogs pretreated with cocaine, or in untreated dogs if the vasopressor agent was oxymetazoline instead of noradrenaline. A possible cause of `self-limiting' blockade is discussed.

5. In doses higher than those required for either α- or β-adrenoceptor blockade, AH 5158 produced effects on cardiac muscle that are attributable to membrane-stabilizing activity. This was manifested as a negative inotropic action in spinal dogs and in guinea-pig left atrial strips, as a negative chronotropic action in syrosingopine pre-treated dogs, and as an increase in the effective refractory period of guinea-pig left atrial strips. AH 5158 was 3-11 times less potent than propranolol in these tests.

6. In open chest dogs AH 5158 resembled propranolol in reducing cardiac output, rate and contractility, effects which are attributable to β-adrenoceptor blockade. The drug differed from propranolol in decreasing rather than increasing total peripheral resistance and in causing larger decreases in arterial blood pressure at equipotent β-adrenoceptor blocking doses. These differences are attributable to the α-adrenoceptor blocking actions of AH 5158.

7. In anaesthetized dogs, intravenously administered AH 5158 antagonized both catecholamine and ouabain-induced arrhythmias. Orally administered AH 5158 lowered systolic arterial pressure in conscious renal hypertensive dogs.

8. These results show AH 5158 to possess a novel profile of activity. Possible uses of the drug in cardiovascular disorders such as hypertension, angina pectoris and cardiac arrhythmias are discussed.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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