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Biomedical subjects

R N Boyes

Publications and source records attributed to R N Boyes.

4 recordsLinked to original sources

New antiarrhythmic agents. 1. Primary alpha-amino anilides.

Thirty-two alpha-amino anilides with various substituents in the aromatic ring and in the alpha position are described. Their abilities to protect mice against chloroform-induced fibrillation and to elicit toxicity were determined. Substitution of an alkyl or aryl group in the alpha position enhanced the antifibrillatory activity. In most cases, increased potency was accompanied by increased toxicity. Eleven compounds were tested in dogs with surgically induced myocardial infarction; most showed antiarrhythmic activity. 2-Aminopropiono-2',6'-xylidide, tocainide, was chosen for clinical investigation.

Anilides

Pharmacokinetic and clinical pharmacological studies with mepivacaine and prilocaine.

The tolerance and pharmacokinetic properties of mepivacaine and prilocaine were compared following i.v. infusion of 250 mg (0.88 and 0.97 mmol respectively) of each drug in five healthy volunteers. Side-effects were minor and occurred in only two subjects during the infusion of mepivacaine. Plasma concentrations of mepivacaine were greater in each subject than the corresponding values for prilocaine. The elimination half-life of mepivacaine was generally longer than that for prilocaine, whereas the total body clearance of prilocaine was consistently greater than the corresponding value for mepivacaine. For each subject the clearance of prilocaine substantially exceeded normal heptic blood flow and therefore an extra-hepatic site of metabolism of prilocaine has been postulated.

Adult

Cardiovascular effects of prenalterol (H133/22) in normal man.

1 Prenalterol, (S-(-)-1-(4 hydroxyphenoxy)-3-isopropylaminopropanol-2 hydrochloride) a cardio-selective beta-adrenergic receptor agonist, was infused intravenously into six normal male volunteers to determine the cardiovascular effects of this drug. 2 On different occasions, each volunteer received a placebo infusion, an infusion of 0.5 mg prenalterol and an infusion of 1 mg prenalterol. Cardiac output (impedance cardiography), arterial pressure (sphygmomanometry), heart rate and ECG were measured throughout. 3 Prenalterol produced a statistically significant increase in cardiac output and at the end of the infusion this increase was 24% with 0.5 mg and 29% with 1 mg, mainly due to an increase in stroke volume (18% and 17%) with a lesser change in heart rate (+2 and +7 beats/min). Pulse pressure increased but mean arterial pressure showed little change. Peripheral resistance fell by 18% and 20%. As indicated by systolic time indices myocardial contractility increased. 4 Prenalterol at plasma concentrations in excess of 20 nmol l-1 produced significant inotropic effects but did not markedly increase heart rate at concentrations of 60 nmol l-1.

Adrenergic beta-Agonists