Membrane stabilization and cardiac effects of d,1-propranolol, d-propranolol and chlorpromazine

Langslet, A

doi:10.1016/0014-2999(70)90174-3

Cited by 77 publications

(26 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since this same pattern occurred in the catecholamine-depleted dogs after the higher doses of drug, the effects must be due to some other property of the drug. This could be membrane stabilization (Langslet, 1970;Fitzgerald et al, 1971). There was no statistically significant change in blood pressure until after 13'25 mg/kg in either normal or depleted dogs and the fall then observed presumably reflects the marked depression of ventricular function.…”

Section: Discussionmentioning

confidence: 98%

Pharmacology of 4‐hydroxypropranolol, a metabolite of propranolol

Fitzgerald¹,

O’Donnell

1971

British J Pharmacology

137

View full text Add to dashboard Cite

Summary1. 4-Hydroxypropranolol, a metabolite produced after oral administration of propranolol, has been shown to be a /3-adrenoceptor blocking drug. It is of similar potency to propranolol in antagonizing the effects of isoprenaline on heart rate and blood pressure in cats and against isoprenaline protection of guinea-pigs from bronchospasm. It is not cardioselective. 2. In rats depleted of catecholamine 4-hydroxypropranolol produced an increase in heart rate, suggesting that it has intrinsic sympathomimetic activity. 3. In anaesthetized dogs 4-hydroxypropranolol produced a decrease in heart rate and dP/dt and an increase in A-V conduction time at doses within the range 0 09-1 25 mg/kg. These effects are a result of /3-adrenoceptor blockade. In dogs depleted of catecholamines these same doses produced an increase in heart rate and dP/dt and a decrease in A-V conduction time. These responses were antagonized by propranolol, and were due to the intrinsic sympathomimetic activity of the compound. At higher doses (5-25 and 13'25 mg/kg) a further dose dependent decrease in heart rate and dP/dt and an increase in A-V conduction time occurred. This trend was also seen in animals depleted of catecholamines. These changes represent membrane stabilizing activity of 4-hydroxypropranolol.4. 4-Hydroxypropranolol is a potent /8-adrenoceptor blocking drug with both intrinsic sympathomimetic activity and membrane stabilizing activity.

show abstract

Section: Discussionmentioning

confidence: 98%

Pharmacology of 4‐hydroxypropranolol, a metabolite of propranolol

Fitzgerald¹,

O’Donnell

1971

British J Pharmacology

137

View full text Add to dashboard Cite

show abstract

“…,-Adrenoceptor blockade however results in a considerable fall in heart rate. This could indicate either that there is a positive chronotropic drive to the heart mediated by P-adrenoceptors or, in the light of the known membrane stabilizing effect of propranolol (Langslet, 1970;, that the drug is reducing the spontaneous rate of depolarization of the pacemaker cells. Since both hexamethonium, which has no reported quinidine-like action, and depletion of catecholamines from the heart (Barrett & Carter, 1970) Cardiac output.…”

Section: Discussionmentioning

confidence: 99%

Responses of the Cardiovascular System of the Rat to Noradrenaline Infusions and Their Modification by Adrenoceptor Blocking Agents

Imms

Neame

Powis

1977

British J Pharmacology

View full text Add to dashboard Cite

The effects of noradrenaline upon the cardiovascular system of the rat, anaesthetized with pentobarbitone, have been investigated. Noradrenaline produces a dose‐dependent increase in mean arterial blood pressure (MABP) which is due entirely to an increase in cardiac output; total peripheral vascular resistance (TPR) remains unchanged. Following β‐adrenoceptor blockade the pressor response to infused noradrenaline is enhanced and is now due mainly to an increase in TPR; the increment in cardiac output is reduced. After α‐adrenoceptor blockade the pressor response is greatly reduced; the residual increase in MABP is due solely to an increase in cardiac output. After ganglion blockade resting cardiac output and TPR both fall, resulting in a reduction in MABP. The pressor response to noradrenaline is enhanced and is now due to increases in both TPR and in cardiac output. The cardiovascular response of the anaesthetized rat to noradrenaline can be explained in terms of classical α‐ and β‐adrenoceptor stimulation by the amine; the unusual form of the response may be due to an effective predominance of β‐adrenoceptor‐mediated effects in this species. It is suggested that the failure of exogenous noradrenaline to produce a rise in TPR results from a balance between the α‐adrenoceptor‐mediated increase and β‐adrenoceptor‐mediated decrease in this variable. However, this proposed balance is lost if resting vasoconstrictor tone is reduced by ganglion blockade.

show abstract

“…(Fitzgerald, 1969;Langslet, 1970 Davis, 1970) and 'quinidine-like' activity on cardiac muscle as represented, for example, by characteristic alterations in the cardiac action potential (Vaughan Williams, 1966), a reduction in maximal driving frequency (Dawes, 1946;Sekiya & Vaughan Williams, 1963) and direct negative inotropic activity (Blinks, 1967;Nayler, Chipperfield & Lowe, 1969). Some properties of propranolol and AH 5158 arising from membrane stabilization were measured in the following experiments:…”

Section: Specificity Of the Adrenoceptor Blocking Actions Of Ah 5158 mentioning

confidence: 99%