An analysis of selective beta receptor blockade

1The actions of five 1-adrenoceptor antagonists, chosen because of reported differences in their selectivities, were compared using the positive chronotropic, vasodepressor and bronchodilator responses to isoprenaline in anaesthetized dogs. 2 Propranolol was a potent antagonist of the isoprenaline responses in all three systems. 3 Practolol and acebutolol (M & B 17,803) blocked the positive chronotropic responses to isoprenaline to a greater extent than the vasodepressor or bronchodilator responses. 4 Butoxamine and a-methyl dichloroisoprenaline showed the opposite selectivity, blocking the vasodepressor and bronchodilator responses to isoprenaline to a greater extent than positive chronotropic responses. However, both drugs were considerably less potent than the other antagonists studied and their selectivities were less clear-cut than those of practolol or acebutolol. 5 All the antagonists lowered the resting heart rate and to a lesser extent the diastolic blood pressure. The effects of propranolol, practolol and acebutolol on heart rate probably result from cardiac f-adrenoceptor blockade. With butoxamine and a-methyl dichloroisoprenaline, however, the effects on heart rate probably result from a direct cardiodepressant action. 6 The relevance of the results to the problem of the sub-classification of ,B-adrenoceptors is discussed.

Section: Discussionmentioning

confidence: 55%

The SELECTIVITY OF Β‐ADRENOCEPTOR ANTAGONISTS ON CARDIOVASCULAR AND BRONCHODILATOR RESPONSES TO ISOPRENALINE IN THE ANAESTHETIZED DOG

Daly¹,

Flook²,

Levy³

1975

“…The pA2 values for H35/25, a f2-selective antagonist (Levy & Wilkenfeld, 1969) were higher than those found for relaxation and inhibition of antigen-induced release of histamine in guinea-pig lung (Van der Heijden & Zaagsma, 1979). Practolol, a l,-selective antagonist (Dunlop & Shanks, 1968), antagonized salbutamol competitively and gave a pA2 value at the top end of the range for tissues containing predominantly #f2-adrenoceptors (Table 3).…”

Section: Resultsmentioning

confidence: 74%

CHARACTERIZATION OF THE RECEPTOR MEDIATING THE ANTI‐ANAPHYLACTIC EFFECTS OF β‐ADRENOCEPTOR AGONISTS IN HUMAN LUNG TISSUE in vitro

Butchers

Skidmore

Vardey

et al. 1980

“…All of these compounds possess an a-methyl group on the ethanolamine side chain and this substituent group appears to be of some significance in the selectivity of /8-adrenoceptor blockade produced by butoxamine and the other members of this group. The significance of the a-methyl substitution is further indicated by the observation that 1-(4'-methylphenyl)-2-isopropylamino ethanol (H 29/50), an agent which differs from H 35/25 in that it does not possess the a-methyl group, is a non-selective /8-adrenoceptor antagonist (Levy & Wilkenfeld, 1969). A similar relationship has been reported for dichloroisoprenaline and its a-methyl analogue (Van Deripe & Moran, 1965).…”

Section: Introductionmentioning

confidence: 99%

The β‐adrenoceptor blocking properties of the α‐methyl analogues of propranolol and practolol in the anaesthetized dog

Lévy

1973

Summary1. The /8-adrenoceptor blocking properties of a-methyl propranolol and a-methyl practolol were determined in anaesthetized dogs according to their abilities to modify the isoprenaline-induced effects on diastolic pressure, heart rate, myocardial contractile force, femoral arterial blood flow and pulmonary airway resistance. 2. a-Methyl propranolol shifted the isoprenaline dose-response curves for the fall in diastolic pressure and the positive inotropic and chronotropic responses to the right in a parallel manner yielding pA2 and slope values of 6'66 (092), 6-34 (0 77) and 6-59 (0-61) respectively. The slopes of the graphs for determining pA2 values for the cardiac p-adrenoceptor blocking properties of amethyl propranolol were significantly less than 1 and indicated a mechanism other than simple, competitive, reversible antagonism. 3. a-Methyl propranolol exerted a much weaker blockade of respiratory smooth muscle /8-adrenoceptors than has been reported for propranolol.