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A series of 4-hydroxy-3-quinolinecarboxamides has been synthesized and evaluated by the oral route as antiinflammatory agents in carrageenin-induced foot edema and adjuvant-induced arthritis and as analgesic agents in the acetic acid induced writhing test. Among the most active molecules, some have shown both analgesic and acute antiinflammatory activities. Others, such as compounds 24, 37, and 52, were only powerful peripherally acting analgesics. Compound 52, being active at 1 mg/kg (ED50), is the most potent compound in the series. Some analogues, substituted in the 2-position by an alcohol, ester, or amine function, displayed potent antiarthritic activity in the same range as that of piroxicam and were also active in acute tests of inflammation and nociception. They inhibited the activity of both cyclooxygenase and 5-lipoxygenase at micromolar concentrations. Compound 102 (RU 43526) showed potent antiarthritic activity (adjuvant-induced arthritis, ED50 = 0.7 mg/kg, po) and gastrointestinal tolerance (ED100 greater than 250 mg/kg, po) and thus it is presently undergoing an extensive pharmacological evaluation.

After trandolapril treatment, the regression of VPB incidence not only is linked to hypertrophy and fibrosis, but additional causal factors also are involved including the myocardial phenotype and new calcium metabolism. Our model of Holter monitoring in conscious middle-aged SHR and multivariate data analysis might be useful in correlating myocardial structural modifications and ectopic activity.

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The effects of opiates on vasopressin secretion have been controversial for many years. This is probably due to the existence of different types of opioid receptors and to the lack of specificity of the compounds used. Specific ĸ agonists, which have been described recently, produce a marked diuretic effect without any associated increase in electrolyte elimination. They seem to exert their effects through an interaction with ĸ receptors situated on nerve terminals and/or pituicytes. These receptors could be directly coupled to L-type calcium channels, their activation leading to a decrease in the effectiveness of action potentials to evoke vasopressin secretion from nerve terminals in the neurohypophysis. This mechanism of action may explain the decrease in plasma vasopressin levels induced by ĸ agonists.

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