Adrenoceptors classification

Ford APDW, Williams TJ, Blue DR, Clarke DE. oq-Adrenoceptor classification sharpening Occam s razor. Trends Pharmacol Sci 1994 15 167-170. 

Ford AP, Arredondo NF, Blue DR Jr, et al. RS-17053 (W - [ 2 - (2-c y c lop rop y I -methoxyphenoxy)ethyl] -5-chloro-a, a-dimethyl- lH-indole-3-ethanamine hydrochloride), a selective a1A-adrenoceptor antagonist, displays low affinity for functional ct -adrenoceptors in human prostate implications for adrenoceptor classification. Mol Pharmacol 1996 49 209-215. 

The discovery of subclasses of adrenergic receptors and the ability of relatively small molecule drugs to stimulate differentially or block these receptors represented a major advance in several areas of pharmacotherapeutics. An excellent review of the development of adrenoceptor classifications is available in Hiebel et al. (47). 

Ford, A.P.. Arredondo. N.F., Blue, D.R. Jr., Bonhaus, D.W., Jasper, J., Kava, M.S.. Lesnick, J., Pfuster, J.R., Shieh, I.A., Vimont, R.L., Williams, T.J., McNeal, J.E., Stamey, T.A., Clarke, D.E., 1996. RS-17053, (W-[2-(2-cyclopropylmethoxi-phenoxy)ethyl]-5-chloro-al-pha, alpha-dimethyl-1 /f-indole-3ethanamine hydrochloride), a selective a, -adrenoceptor antagonist, displays low affinity for functional a I-adrenoceptors in human prostate implications for adrenoceptor classification. Mol. Pharmacol. 49, 209-215. 

Timmermans PB, van Zwieten PA. a2-Adrenoceptors classification, localization, mechanisms, and targets for drugs. J Med Chem 1982 25 1389-1401. 

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

Ahlquist, in 1948, first proposed that noradrenaline could produce its diverse physiological effects by acting on different populations of adrenoceptors, which he termed a and ft receptors. This classification was based upon the relative selectivity of adrenaline for the a receptors and isoprenaline for the ft receptors drugs such as phentolamine were found to be specific antagonists of the a, and propranolol for the ft receptors. 

Similar classifications are used for other receptors. For example, adrenoceptors are classified as a and P sub-types. These sub-types are further classified according to the nature of their exogenous ligands. The various types are distinguished by the use of subscript numbers. 

The biological effects of epinephrine and norepinephrine are mediated by nine different adrenoceptors (a1A,B,D, a2A,B,c. Pi, P2. P3)-To date, only the classification into a-i, a2, pi and p2 receptors has therapeutic relevance. 

Classification of sympathomimetics by mode of action and selectivity for adrenoceptors... 

The absence of an alc-adrenoceptor, as with the absence of the 5-HTlc receptor, may serve as a reminder that the classification of receptors is a nasty business."... 

Bylund DB, Bond RA, Clarke DE, et al. Adrenoceptors. In Vanhoutte PM, et al., editors. The IUPHAR Compendium of Receptor Characterization and Classification. London IUPHAR Media, 1998 58-74. 

Classification The sympathomimetics are direct or indirect adrenoceptor agonists and are subdivided in two ways by mode of action and by spectrum of action (Figure 9-1). 

A. Classification and Prototypes Ketanserin is a S-HT and alpha-adrenoceptor blocker. Phe-noxybenzamine (an alpha-adrenoceptor blocker) and cyproheptadine (an Hj blocker) are also good 5-HTj blockers. Ondansetron, granisetron, dolasetron, and alosetron are 5-HTj blockers. The ergot alkaloids are partial agonists at 5-HT and other receptors (see below). 

From a historical point of view ergot alkaloids are closely linked to the classification of adrenoceptors into two major subtypes (a and / ). The discrimination between a- and -adrenoceptors was based on the insensitivity of the latter to ergot alkaloids or -haloalkylamines (Nickerson, 1949). On the basis of structural, transductional, and operational criteria it became apparent that the existence of two subtypes of a-adrenoceptors, the ai-adrenoceptor, sensitive to blockade by prazosin, and the a2-adrenoceptor, sensitive to blockade by yohimbine or rauwolscine, makes it more appropriate to classify adrenoceptors into three major subtypes the aj-adrenoceptors, az-adrenoceptors, and -adrenoceptors (Bylund, 1988). 

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