Adrenoceptors pharmacology

Koshimizu T etal Recent progress in alphai-adrenoceptor pharmacology. Biol Pharm Bull 2002 25 401. [PMID 11995914]... 

Central and peripheral a-adrenoceptors. Pharmacological aspects and clinical potential, 13, 209... 

Daniels DV, Gever JR, Jasper JR, et al. Human cloned a1A-adrenoceptor isoforms display a1L-adrenoceptor pharmacology in functional studies. Eur J Pharmacol 1999 370 337-343. 

Kaumann AJ, Engelhardt S, Hein L, Molenaar P, Lohse M. Abolition of (-)-CGP 12177-evoked cardiostimulation in double [1,/[12-adrenoecptor knockout mice. Obligatory role of p,-adrenoceptors for putative p4-adrenoceptor pharmacology. Naunyn Schmiedebergs Arch Pharmacol 2001 363 87-93. 

Bylund DB. Subtypes of -adrenoceptors pharmacological and molecular biological evidence converge. Trends Pharmacol Sci 1988 9 356-361. 

Esmolol is iv adrninistered. Maximal P-adrenoceptor blockade occurs in 1 min. Its elimination half-life is about 9 min. EuU recovery from P-adrenoceptor blockade is within 30 min after stopping the infusion. The therapeutic plasma concentrations are 0.4—1.2 lg/mL. It is metabolized by hydrolysis in whole blood by red blood cell esterases resulting in the formation of a primary acid metabohte and free methanol. The metabohte is pharmacologically inactive. The resulting methanol levels are not toxic. Esmolol is 55% bound to plasma protein, the acid metabohte only 10%. Less than 2% of parent dmg and the acid metabohte are excreted by the kidneys. Plasma levels may be elevated and elimination half-hves prolonged in patients with renal disease (41). 

Regulation of transmitter release does not rest solely on the frequency at which nerve impulses reach the terminals. Early experiments using stimulated sympathetic nerve/end-organ preparations in situ, or synaptosomes, indicated that release of [ HJnoradrenaline was attenuated by exposure to unlabelled, exogenous transmitter. This action was attributed to presynaptic adrenoceptors, designated a2-adrenoceptors, which were functionally distinct from either aj- or )S-adrenoceptors. Later experiments have confirmed that ai-adrenoceptors comprise a family of pharmacologically and structurally distinct adrenoceptor subtypes. 

A second pathway, uveoscleral outflow, comprises the other 20% of aqueous humor drainage. In the uveoscleral pathway, aqueous humor exits the anterior chamber through the iris root and through spaces in the ciliary muscles, which then drains into suprachoroidal space. Uveoscleral outflow can be pharmacologically modulated by adrenoceptors, prostanoid receptors, and prostamide receptors.4,10,12-15... 

Ko FN, Yu SM, Su MJ, Wu YC, Teng CM. Pharmacological activity of (-)-discreta-mine, a novel vascular alpha-adrenoceptor and 5-hydroxytryptamine receptor antagonist, isolated from Fissistigma glaucescens. BrJ Pharmacol. 1993 110 882-888. 

Hoffman, B.B., Adrenoceptor-activating and other sympathomimetic drugs, in Basic and Clinical Pharmacology, 8th ed., Katzung, B.G., Ed., Lange Medical Books/McGraw-Hill, New York, 2001, chap. 9. 

The renaissance of the Biginelli MCR can be attributed to the obtained pyrimidine derivatives, which show remarkable pharmacological activity. A broad range of effects, including antiviral, antitumor, antibacterial, anti-inflammatory as well as antihypertensive activities has been ascribed to these partly reduced pyrimidine derivatives [96], such as 9-117 and 9-118 (antihypertensive agents) [97] and 9-119 (ala-adrenoceptor-selective antagonist) [98] (Scheme 9.24). Recently, the scope of this pharmacophore has been further increased by the identification of the 4-(3-hydroxyphenyl)-pyrimidin-2-thione derivative 9-120 known as monastrol [98], a novel cell-permeable lead molecule for the development of new anticancer drugs. Monastrol appears specifically to affect cell division (mitosis) by a new mechanism,... 

Hieble, J. P., Bylund, D. B., Clarke, D. E. etal. International Union of Pharmacology. X. Recommendation for nomenclature of alpha 1-adrenoceptors consensus update. Pharmacol. Rev. 47 267-270,1995. 

Membrane-associated receptors are linked to transducing proteins (like G-proteins) in the inner portion of the membrane. G-protein coupled receptor (GPCR) families comprise a major class of the receptors that are pharmacologically relevant, such as muscarinic acetyl choline receptors, adrenoceptors, dopamine receptors, serotonine, opiate, peptide hormone, purinerg receptors, and also sensory chemoreceptors. A large variety of subtypes are described in the pharmacological literature. 

Hancock, A.A. (1996) a 1-Adrenoceptor adrenoceptor subtypes a synopsis of their pharmacology and molecular biology. Drug Development Research, 39, 54-107. 

Michel, M.C., Kenny, B. and Schwinn, D. A. (1995) Classification of alpha 1-adrenoceptor subtypes. Naunyn-Schmiedebergs Archives of Pharmacology, 352, 1-10. 

Leonardi, A., Motta, G., Boi, C., Testa, R., Poggesi, E., De Benedetti, P.G. and Menziani, M.C. (1999) Synthesis, pharmacological evaluation, and structure-activity relationship and quantitative structure-activity relationship studies on novel derivatives of 2,4-diamino-6,7-dimethoxy-quinazoline alphal-adrenoceptor antagonists. Journal of Medicinal Chemistry, 42, 427-437. 

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