Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0600097 (Sedation)
 1,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The acute toxicity of 6-(3-[4-(o-methoxyphenyl)-1-piperazinyl-propylamino)-1,3-dimethyluracil (urapidil, Ebrantil) was tested in rats and mice using oral and intravenous routes. The tolerance upon repeated oral administration was tested in subacute and chronic toxicity studies lasting 3 weeks, 3, 6 and 12 months in the rat, as well as studies lasting 4 weeks and 6 months in the dog. The effect of urapidil on the reproduction in mice, rats and rabbits was also investigated. Sedation is seen in mice and rats after a single administration of urapidil, at lethal doses, tremor and convulsions appear. The same symptoms were seen in experiments with repeated oral administration in the rat (stomach tube) or in the dog (tablets) as the criterium of tolerance. In feeding studies in the rat, the decreased body weight gain was the criterium of toxicity. The no-effect dose in the rat is 42 times the therapeutic dose in man. The no-effect dose in the dog lies between 8 and 21 times the average therapeutic dose. An inhibition of the estrus cycle in the rat proved to be species-specific. In reproductin studies, significant toxic effects were seen besides functional disturbances specific to the rat. Urapidil was not teratogenic. The development and reproductive capacity of the F1-generation was not affected.
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PMID:[Toxicologic study on the antihypertensive agent urapidil]. 57 2

Antihypertensive activity can be induced by the following types of drugs: alpha-adrenoceptor antagonists; beta-adrenoceptor antagonists (beta-blockers); and alpha 2-adrenoceptor agonists (in the central nervous system). After a general survey of peripheral and central alpha- and beta-adrenoceptors, including their modern classification and subdivision, attention was paid to the various drugs with antihypertensive activity based upon interaction with various alpha- and beta-adrenoceptors. Of the peripheral alpha-adrenoceptor blockers, only those selective for alpha 1-adrenoceptors are useful antihypertensives. Prazosin and its successors (doxazosin, terazosin, trimazosin) are the best-known examples of such drugs. Their mode of action, and the low incidence and degree of reflex tachycardia, can be satisfactorily explained on the basis of alpha 1-adrenoceptor blockade in the periphery and possibly also in the CNS. Urapidil is a selective alpha 1-adrenoceptor blocker with an additional central component not based upon interaction with alpha-adrenoceptors. With respect to centrally acting alpha 2-adrenoceptor agonists, clonidine, guanfacine and alpha-methyldopa are the prototypes. Their antihypertensive activity is triggered by the stimulation of central alpha 2-adrenoceptors in the brain stem, causing reduced peripheral sympathetic activity and hence a fall in blood pressure and heart rate. Sedation, a common side effect of these drugs, is assumed to be mediated by alpha 2-adrenoceptors at cortical sites. Although beta-adrenoceptor blocking agents (beta-blockers) are widely and successfully used as antihypertensives, their mode of action is still poorly understood, only hypotheses being available at present. However, their side effects can be rationally explained on the basis of beta-adrenoceptor blockade.
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PMID:Antihypertensive drugs interacting with alpha- and beta-adrenoceptors. A review of basic pharmacology. 284 Oct 84