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Antiarrhythmic effect of solvents: propylene glycol, benzyl alcohol.

Propylene glycol and benzyl alcohol, the main constituents of most solvent vehicles, display a pronounced antiarrhythmic-antifibrillatory effects, when injected intravenously into animals (dogs, rats) with spontaneous or drug-induced arrhythmias. The antiarrhythmic dose for propylene glycol amounts to 0.2-0.3 ml/kg of a 70 per cent solution and, for benzyl alcohol to 0.2-0.4 ml/kg of a 4 per cent solution in physiologic saline, respectively. Similar effects were also obtained by the combined injection of propylene glycol + benzyl alcohol, in proportions which correspond to the formulae of numerous commercial "solvents" (vehicles): 2 to 20 per cent solutions of benzyl alcohol in 70 per cent propylene glycol (0.05-0.2 ml/kg). The mechanisms which might be responsible for the antiarrhythmic activity of solvents are discussed: lengthening of the effective refractory period, local and general anaesthetic effects, changes of osmolarity. The intravenous injection of propylene glycol and/or benzyl alcohol, in high doses, produces intravascular haemolysis. Clinical investigations are recommended as to the potential, beneficial or toxic effects of drug solvents, especially upon the cardiocirculatory system.

Animals↗

Structure-activity profile of substituted purines and inflammation in the delayed hypersensitivity skin reaction.

Substituted purines were tested for their effectiveness in inhibiting the delayed hypersensitivity skin reaction (DHSR) caused by tuberculin in the guinea-pig. Among the tested purines were naturally occurring derivatives of guanine and adenine, including cyclic AMP. Based on the structure-activity profile, a class of purines was identified, the members of which were very effective inhibitors of inflammatory aspects of the DHSR and are characterized by a benzyl group in position 9, an amino or alkylamino group in position 6, and various substituents in position 2. This class of 2-substituted-9-benzyladenines was more effective in the DHSR than some antimetabolites, particularly the structurally related mercaptopurines.

Adenine↗

Double-blind dose-response multicenter comparison of fedotozine and placebo in treatment of nonulcer dyspepsia.

The efficacy and safety of the peripheral kappa-receptor agonist fedotozine was investigated in a double-blind, placebo-controlled, dose-ranging study involving 146 patients with nonulcer dyspepsia (NUD). After a two-week washout, patients were assigned to one of four groups to receive either placebo or fedotozine three times a day at doses of 10, 30, or 70 mg for six weeks. Analysis of mean symptom intensity scores showed that the 30-and 70-mg doses of fedotozine were superior to placebo in relieving postprandial fullness, bloating, abdominal pain, and nausea. Eructation and early satiety were marginally affected. The 30-mg dose was significantly more effective than placebo in reducing the total symptom score. Eight-two mostly minor adverse effects were recorded, but no significant differences in distribution emerged between placebo and treatment groups. The number of withdrawals declined significantly as a function of increasing dose. These results indicate that 30 mg three times a day is the minimal effective dose of fedotozine in the treatment of NUD symptoms and that this treatment is safe.

Adult↗