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2-Amino-5-mercapto-1,3,4-thiadiazole was condensed with various 6-substituted 2-phenylbenzoxazin-4 (3H)-ones to yield the compounds 1. When these compounds were subjected to mercaptoetherification the title compounds 2 4 were obtained. They were screened for their antitubercular activity against Mycobacterium smegmatis and Mycobacterium tuberculosis H3, Rv in vitro. Structure-activity relationships were established. 0365-6233/83/0909M59 $ M.50/0 O Verlag Chemie GmbH, Weinheim 1983 Kumar and CoworkersArch. Pharm.

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The effects of microinjection of histamine and its antagonists into mesencephalic nucleus dorsalis raphe, were investigated on mean arterial pressure and heart rate in cats to elucidate the nature and role of histaminergic receptors in cardiovascular regulation. Microinjection of histamine (5 and 10 micrograms) into nucleus dorsalis raphe elicited both inhibitory and excitatory cardiovascular responses respectively. On the other hand, microinjection of H2-receptor blocker, cimetidine (10 micrograms) resulted in hypertension and tachycardia while H1-receptor antagonist, mepyramine (10 micrograms) microinjection evoked hypotension and bradycardia. Furthermore, local pretreatment with cimetidine and mepyramine blocked the inhibitory and excitatory cardiovascular responses of graded doses of histamine microinjection. These H1 and H2 receptors are localized in nucleus dorsalis raphe since microinjection of histamine into adjoining neural structures did not evoke any cardiovascular change. Furthermore, both the inhibitory and excitatory cardiovascular responses to histamine microinjection could not be observed in animals with spinal cord transection and in animals pretreated with p-chlorophenylalanine while they could be observed in bilateral cervical vagotomized animals. Thus, it appears that these cardiovascular responses to microinjection of histamine into nucleus dorsalis raphe, are due to modulation of serotonergic bulbospinal influence on sympathetic preganglionic neurones in the spinal cord. Moreover, the excitatory cardiovascular responses of high dose of histamine (10 micrograms) seem to result from a local release of noradrenaline since they were blocked by prior microinjection of guanethidine and piperoxan into nucleus dorsalis raphe. A release of noradrenaline in turn, modulates the activity of the neurones of the nucleus by acting on alpha adrenoceptors and thereby alters the activity of sympathetic preganglionic neurones.(ABSTRACT TRUNCATED AT 250 WORDS)

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