Arzneimittel Forsch
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Arzneimittel Forsch · Jan 1984
A quantitative analysis of steric and hydrophobic effects in ribonucleoside diphosphate reductase inhibition by thiosemicarbazones.
Ribonucleoside diphosphate reductase (RDR) inhibitory activity of 2-formylpyridine and 1-formylisoquinoline thiosemicarbazones is quantitatively analysed in relation to a steric parameter (van der Waals volume, VW) and the hydrophobic parameter logP. The activity is found to be significantly correlated with VW and very poorly with logP. On the basis of this, it is inferred that RDR inhibition by thiosemicarbazones is very sensitive to steric effects and is little influenced by the hydrophobic character of the molecules.
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Arzneimittel Forsch · Jan 1984
2-Acetylpyridine thiosemicarbazones. 10. 2-Propionyl-, 2-butyryl-, and 2-(2-methylpropionyl)pyridine thiosemicarbazones as potential antimalarial agents.
In view of the antimalarial properties observed for many 2-acetylpyridine thiosemicarbazones, a series of N4,N4-disubstituted thiosemicarbazones derived from 2-propionyl-, 2-butyryl-, and 2-(2-methylpropionyl)pyridine was prepared for evaluation against the malaria parasite, Plasmodium berghei, in the mouse. The thiosemicarbazones were made by the reaction of methyl hydrazinecarbodithioate with a 2-acylpyridine to give the intermediate methyl 3-[1-2-pyridinyl)alkylidene]hydrazinecarbodithioates. ⋯ The three thiosemicarbazones derived from 3-azabicyclo[3.2.2]nonane were most effective, the greatest potency being exhibited by 3-azabicyclo-[3.2.2]nonane-3-thiocarboxylic acid 2-[1-(2-pyridinyl)butylidene]hydrazide (4) which cured 4/5 mice at a dose of 160 mg/kg. In contrast to the related thiosemicarbazones derived from 2-acetylpyridine, virtually no toxic effects were observed in the series described here.
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Arzneimittel Forsch · Jan 1983
Randomized Controlled Trial Comparative Study Clinical Trial[A controlled clinical single-dose comparative study of suprofen and diflunisal].
In a single-dose, double-blind randomized study, the analgesic efficacy of suprofen 200, suprofen (alpha-methyl-4-(2-thienylcarbonyl)-benzene acetic acid; Suprol) 400 mg and diflunisal 750 mg capsules was determined in comparison to placebo capsules. A total of 130 patients participated in the study, all of them requiring analgesic treatment on the first post-operative day following meniscectomy. ⋯ Despite great differences in dosage and half-life, the active test substances must be regarded as equipment. Side effects were reported by 2 patients each in the diflunisal 750 mg and the placebo group, and by 1 patient treated with suprofen 200 mg.
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Arzneimittel Forsch · Jan 1983
Randomized Controlled Trial Clinical Trial[Treatment of postoperative wound pain with suprofen].
The present randomized double-blind study was performed to investigate the analgesic effects of single doses of suprofen (alpha-methyl-4-(2-thienylcarbonyl)benzene acetic acid; Suprol) 200 mg, suprofen 400 mg paracetamol (APAP, acetaminophen) 650 mg, and combination suprofen 100 mg + APAP 650 mg versus placebo. The five treatment groups were homogeneous as to their demographic features and comprised 28--32 subjects each. Data for a total of 146 patients were evaluated. ⋯ Suprofen 200 mg ranked third. Statistical significance was only seen for the parameter pain intensity (SPID) on comparison of suprofen 100 mg + APAP 650 mg versus suprofen 200 mg. Side effects, homogeneously distributed over the treatment groups, were observed in four cases.
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The antiarrhythmic, local anesthetic and acute local and systemic toxic effects of DL-N-(2-hydroxyethyl)-pipecolinyl-2,6-dimethylanilide (AL-S-1249, droxicainide) and lidocaine were compared in animals. When given intravenously both substances suppressed ouabain-induced arrhythmias in pentobarbital-anesthetized guinea pigs; they were equipotent in this regard and had the same duration of antiarrhythmic action. ⋯ When given intravenously to unanesthetized mice and unanesthetized and pentobarbital-anesthetized rats, the LD50's for droxicainide were consistently higher than those for lidocaine. Since droxicainide has antiarrhythmic and local anesthetic properties that are quantitatively similar to lidocaine but local and systemic toxicity that is relatively weaker, its antiarrhythmic and local anesthetic actions merit further study.