Henry F. Campbell

Pharmacology of RG W-2938 : a cardiotonic agent with vasodilator activity

Summary The cardiovascular effects of RG W-2938, 6-[6-(3, 4-dihydro-3methyl-2(1H)-2-oxoquinazolinyl)]-4, 5-dihydro-3(2H)-pyridazinone, a new nonglycoside, non-catecholamine cardiotonic/vasodilator agent were examined in vivo in anesthetized and conscious dogs and in vitro in isolated guinea pig hearts; in the latter, RG W-2938 5 nmol-5 μmol increased contractility in a doserelated fashion. RG W-2938 30–300 μg/kg administered intravenously (i.v.) to anesthetized dogs increased contractile force while decreasing arterial pressure and total peripheral resistance (TPR) in a dose-related manner. Heart rate (HR) was only slightly increased, and aortic flow was not appreciably altered. A single oral dose of RG W-2938 0.3 mg/kg administered to conscious chronically instrumented dogs produced a marked and sustained increase in contractility 15–240 min after treatment while only slightly increasing HR. The effects of RG W-2938 30–300 μg/kg, i.v. were studied in a mecamylamine-propranplol-induced model of heart failure. RG W-2938 effectively reversed the drug-induced heart failure by increasing myocardial contractility and decreasing arterial pressure while only slightly affecting HR. These studies show that RG W-2938 is an orally effective positive inotropic/vasodilator agent.

3- and 5-amino thiatriazines, and their pharmaceutical uses

A class of 3- and 5-amino thiatriazine compounds exhibiting pharmacological activity, including anti-ulcerogenic and gastrointestinal cytoprotective activity, pharmaceutical compositions comprising these compounds, and methods for the treatment of gastrointestinal hyperacidity and ulcerogenic disorders in mammals using said compositions.