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In vivo and in vitro techniques have been used to study the effect of catecholamines on gastrin release. The i.v. infusion of epinephrine in dogs produced a significant rise in plasma gastrin concentration. This response was prevented by the administration of propranolol to block beta-adrenergic receptors. The infusion of isoproterenol, a beta-adrenergic agonist, produced a significant rise in gastrin levels, while phenylephrine, an alpha-adrenergic agonist, had no effect. In in vitro studies using isolated pieces of rat antrum, isoproterenol stimulated acute phase release of gastrin, whereas phenylephrine was again without effect. The studies indicate that catecholamines directly influence G cell function.

The biotransformation of alinidine (N-allyl clonidine) to clonidine was studied in 5 healthy Sudanese Arabs following acute and chronic administration of alinidine, 40 mg orally for 8 days. The results indicate that a small amount of clonidine is formed; this reached a maximum of 1.0 ± 0.47 ng/ml on day 4 following administration of alinidine, 40 mg 3 times a day. The concentration of clonidine formed from alinidine was not significantly different from that seen in a Caucasian study on healthy volunteers (0.92 ± 0.28 ng/ml) following administration of alinidine, 40 mg twice daily. The side-effects reported most frequently included tiredness, lethargy and dry mouth.

1 The effect of single and repeated oral doses of indoramin 25 mg, prazosin 1 mg and placebo on arterial pressure and heart rate supine, standing and after exercise was studied in five normal volunteers. 2 Each study period lasted four days. Observations were made before, and at 1, 2, 3, 4 and 6 h after drug administration on days 1 and 4. On days 2 and 3, the drugs were administered 8-hourly, and observations made before and 2 h after the morning dose on each day. 3 Neither drug changed arterial pressure or heart rate in the supine position, or after exercise. Neither drug reduced standing diastolic arterial pressure. 4 On day 1, indoramin reduced standing systolic arterial pressure from 119.0±3.4 mm Hg (mean±s.e.mean) to 100.0±10.3 mm Hg at 2 h (P0.05). This reduction was accompanied by a marked increase in standing heart rate, from 85.0±3.9 beats min-1 to 108.8±3.6 beats min-1 at 2 h (P

The cardioselective beta-adrenoceptor blocking agent practolol was used in the management of ventricular and supraventricular dysrhythmias associated with acute myocardial Infarction in 134 patients, and in the management of these dysrhythmias in 19 patients with acute myocardial ischemia. Practolol was frequently effective in controlling ventricular dysrhythmias which occurred within the first 24 hours after the onset of symptoms of acute myocardial infarction. It was also effective in controlling the ventricular dysrhythmias which occurred after resuscitation from ventricular fibrillation. It was of particular value when therapeutic doses of lidocaine had been ineffective. Practolol was much less effective in controlling ventricular dysrhythmias which occurred more than 24 hours after acute infarction. Atrial fibrillation and atrial flutter were infrequently abolished by practolol in undigitalized patients after acute myocardial infarction. There was no correlation between the effectiveness of practolol and the blood concentration of the drug. One adverse effect of practolol was the occurrence of sinus bradycardia with or without an increase in the frequency of ventricular ectopic beats. Bradycardia was sometimes accompanied by hypotension. Severe hypotension occasionally occurred in the absence of bradycardia.

SUMMARY The intravenous injection of isoprenaline and glucagon in anaesthetized dogs increased heart rate and stroke volume. Isoprenaline was 60 and 500 times more potent than glucagon in increasing heart rate and stroke volume respectively. Isoprenaline, but not glucagon, dilated the femoral blood vessels and increased ventricular automaticity. Propranolol blocked the cardiac actions of isoprenaline but not those of glucagon. The actions of glucagon do not appear to be mediated through beta adrenoceptive receptors.

Seventeen patients with thyrotoxicosis have been treated with relatively small doses of iodine-131 and their thyrotoxic symptoms have been controlled with propranolol. This use of propranolol, which does not interfere with thyroid-function tests, may allow an earlier and better differentiation of those patients who will respond effectively to a small dose of therapeutic radioactive iodine.

Plasma-gastrin levels measured by radioimmunoassay were found to be elevated in two patients with phaeochromocytoma. Both the administration of phenoxybenzamine and the later removal of the tumour reduced the fasting plasma-gastrin level to normal. The intravenous infusion of adrenaline in dogs produced a rise in plasma-gastrin level. It is concluded that catecholamines stimulate gastrin release.

The effect of propranolol on radioiodine utilization by the thyroid gland has been studied in 18 patients. All parameters of iodine uptake by the thyroid – initial 5–20 minutes after intravenous administration, 2, 4, 24 and 48 hours after oral administration were unaltered by propranolol administration. In three of four patients studied an increase in isotopically labelled serum PBI was observed after 8 days propranolol therapy.

Propranolol reduced heart-rate in 10 patients with hyperthyroidism by 17.5 beats per minute and in 5 patients with hypothyroidism by 11.4 beats per minute. The heart-rate after propranolol in the two groups was 74.2 and 47.2 beats per minute respectively. The intrinsic heart-rate was greater than expected in 14 of 15 patients with hyperthyroidism and less than expected in 7 patients with hypothyroidism. It was concluded that the differences in heart-rate between patients with hyperthyroidism and hypothyroidism are mainly due to thyroxine acting directly on the heart and not to its potentiation of the action of catecholamines.

The development of scientific medicine during the last 30 years has extended to the study of the effects of drugs in man with the development of the speciality of Clinical Pharmacology.