The HAEMODYNAMIC EFFECTS OF PROLONGED ORAL ADMINISTRATION OF OXYFEDRINE, a PARTIAL AGONIST AT Β‐ADRENOCEPTORS: COMPARISON WITH PROPRANOLOL

Abstract

1Haemodynamic changes have been studied in cats after the chronic oral administration of oxyfedrine (14 mg/kg for 3-4 weeks) or of placebo (lactose). The initial part of the study was carried out under double-blind conditions. The arterial blood pressure was between 19 mmHg (diastolic) and 27 mmHg (systolic) higher in the oxyfedrine treated animals, but there were no differences between the two groups with regard to cardiac output, left ventricular dP/dt max, heart rate or systolic ejection time. 2 In cats similarly treated with propranolol (4 mg/kg) there was a slight (12%), but significant, reduction in cardiac output. 3 Isoprenaline dose-response curves were shifted to the right in the cats administered oxyfedrine as well as in those administered propranolol. The degree of shift was five-fold (positive chronotropic response) and 20-fold (decrease in diastolic blood pressure) in the oxyfedrine group and 10-and 80-fold, respectively, in the propranolol group. 4 In contrast to the partial blockade of the effects of isoprenaline, the haemodynamic response to oxyfedrine was largely unaltered, both in the cats pretreated with propranolol and in those pretreated with oxyfedrine. The pressor response to noradrenaline was potentiated in the cats pretreated with oxyfedrine. 5 These results provide an explanation for the anti-anginal action of oxyfedrine. Some degree of 3-adrenoceptor blockade is achieved without a reduction in cardiac output or left ventricular dP/dt max. The relevance of these findings to the haemodynamic situation in angina is discussed.

THE EFFECT OF INDOMETHACIN ON THE CARDIOVASCULAR AND METABOLIC RESPONSES TO E. coli ENDOTOXIN IN THE CAT

“…*P < 0.0005; **P < 0.005; ***P < 0.025. Parratt, 1973;1974). Endotoxin administration resulted in a substantial metabolic acidosis ( Table 2).…”

Possible mechanisms of action of oxyfedrine as an antianginal drug [letter]

“…Another intriguing question which requires answering is whether, following prolonged administration of oxyfedrine to anginal patients, it loses its agonist properties whilst retaining its antagonist properties at f3-adrenoceptor sites. In a relevant animal study, although admittedly with much larger doses than those used by the Northwich Park group, one of us (Parratt, 1974) found that isoprenaline dose-responses curves were shifted to the right following oral treatment with oxyfedrine for 3-4 weeks (evidence of f8-adrenoceptor blockade) yet there was no reduction in resting cardiac output, left Br. J. clin.…”

The Cardiovascular Pharmacology of 7‐propyl‐theophylline‐dopamine (D4975); Comparison With Dopamine and Dobutamine

“…Four of these variables were also displayed continuously on an oscilloscope (Racal Instruments type 9383). Cardiac output was measured by thermodilution (using simple copper-constantan thermocouples; Parratt, 1974) and the heart rate was measured from the electrocardiogram. Body temperature was recorded from the rectum and mid-oesophagus with direct recording thermocouples (Ellab, Copenhagen).…”

“…Body temperature was recorded from the rectum and mid-oesophagus with direct recording thermocouples (Ellab, Copenhagen). Blood gases, pH and arterial lactate were measured by methods previously described in full (Parratt, 1974 pJkg. The effects of D4975 were also examined before, and 10 to 30 min after the intravenous administration of propranolol (0.25 mg/kg).…”