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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

The acid metabolite of ZD7114 is a partial agonist of lipolysis mediated by the rat beta 3-adrenoceptor.

Experiments were performed to characterise the lipolytic effects of the acid metabolite, ZM215001, ((S)-4-[2-hydroxy-3-phenoxy-propylamino-ethoxy] phenoxyacetic acid) of the putative beta 3-adrenoceptor agonist, ZD7114 ((S)-4-[2-hydroxy-3-phenoxy-propylamino-ethoxy]-N-(2-methoxyethyl) phenoxyacetamide) on isolated rat white adipocytes. ZM215001 was used for these studies since it is the predominant moiety after in vivo administration of ZD7114. The agonist properties of ZM215001 were assessed in comparison to the standard nonselective beta-adrenoceptor agonist (+/-)-isoprenaline and the beta 3-adrenoceptor-selective agonist BRL 37344. Isoprenaline, BRL 37344 and ZM215001 all stimulated the rate of free fatty acid release from isolated adipocytes with the order of potency being BRL > isoprenaline > ZM215001. The maximum effect of BRL 37344 was equivalent to that of isoprenaline, but ZM215001 achieved only 30% of the maximum isoprenaline response. ZM215001 competitively antagonised the lipolytic response to BRL 37344 (pA2 = 7.26), whereas the agonist effects of BRL 37344 were not antagonised competitively by the selective antagonists ICI 118551 and CGP 20712A, at concentrations which would be expected to block beta 1- and beta 2-adrenoceptors respectively. These results indicate that ZM215001 has low intrinsic activity at the rat adipocyte beta 3-adrenoceptor, and is a partial agonist of lipolysis in rat white adipocytes.[1]


  1. The acid metabolite of ZD7114 is a partial agonist of lipolysis mediated by the rat beta 3-adrenoceptor. Mayers, R.M., Quayle, S.P., Thompson, A.J., Grant, T.L., Holloway, B.R. Eur. J. Pharmacol. (1996) [Pubmed]
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