The drug has been found to reversehyperprolactinemia induced by the dopamine D2 receptorantagonistamisulpride without producingcentral effects in rats.[6][7] It has also been found to reduce circulatingnorepinephrine levels by 55% in people with severeheart failure, an action thought to be mediated by its dopamine D2 receptor agonism in the periphery.[4][5][8] This depression in norepinephrine levels was accompanied by improvements in cardiovascular parameters.[4][5]
Carmoxirole was first described in thescientific literature by 1988.[9][10] It is based on the indolyl-3-butylamine framework, a class of dopamine receptor agonists.[11]
^abRemme WJ (December 1994). "Therapeutic strategies and neurohormonal control in heart failure".European Heart Journal. 15 Suppl D:129–138.doi:10.1093/eurheartj/15.suppl_d.129.PMID7713102.Orally active dopaminergic agents are few, i.e. levodopa, ibopamine and carmoxirole. Of these, ibopamine has been studied most extensively.
^abcdeHaeusler G, Lues I, Minck KO, Schelling P, Seyfried CA (September 1992). "Pharmacological basis for antihypertensive therapy with a novel dopamine agonist".European Heart Journal. 13 Suppl D:129–135.doi:10.1093/eurheartj/13.suppl_d.129.PMID1356783.
^abcRemme WJ (March 2001). "Dopaminergic agents in heart failure: rebirth of an old concept".Cardiovascular Drugs and Therapy.15 (2):107–109.doi:10.1023/a:1011162510450.PMID11669402.That DA2 stimulation may lead to a significant reduction in plasma norepinephrine levels in heart failure, was reported already by van der Ent et al. in this journal several years ago [9]. In their study, acute intravenous administration of the selective DA2 agonist carmoxirole decreased circulating norepinephrine by 55% in patients with severe heart failure, accompanied by a significant improvement in cardiac pump function and reduced LV filling pressures.
^abcRemme WJ (December 1995). "Neurohormonal modulation in heart failure: ACE inhibition and beyond".European Heart Journal. 16 Suppl N:73–78.doi:10.1093/eurheartj/16.suppl_n.73.PMID8682065.Activation of neuronal dopaminergic D2 receptors inhibits the release of noradrenaline in the synaptic cleft and reduces sympathetic activity. In addition, activation of D2 receptors in the adrenal cortex results in aldosterone suppression. Selective D2 agonists therefore may be useful in heart failure. Currently, scant data are available in humans. Carmoxirole, a specific D2 agonist, acutely reduces circulating noradrenaline levels; this is accompanied by significant improvements in cardiac pump function, left and right ventricular filling pressures, and circulating atrial natriuretic peptide levels (personal communication, M. Van der Ent).
^Marchese G, Ruiu S, Casti P, Bartholini F, Saba P, Gessa GL, et al. (June 2002). "Carmoxirole is able to reduce amisulpride-induced hyperprolactinemia without affecting its central effect".European Journal of Pharmacology.447 (1):109–114.doi:10.1016/s0014-2999(02)01896-4.hdl:11380/1212095.PMID12106810.
^van der Ent M, van den Heuvel AF, Remme WJ (September 1998). "Neurohumoral response to carmoxirole, a selective dopamine (D2) receptor agonist, in patients with chronic moderate heart failure".Cardiovascular Drugs and Therapy.12 (4):387–394.doi:10.1023/a:1007776918751.PMID9825185.
^Gericke R, Böttcher H (16 August 1988). "Synthese von 3-[4-(1,2,3,6-Tetrahydro-4-phenyl-1-pyridyl)butyl]-5-indolcarbonsäure, eine blutdrucksenkende Verbindung mit neuartigem Wirkprinzip".Liebigs Annalen der Chemie.1988 (8):749–752.doi:10.1002/jlac.198819880807.ISSN0170-2041.
^Haase AF, Greiner HE, Seyfried CA (1991). "Neurochemical profile of EMD 45609 (Carmoxirole), a dopamine DA2-receptor agonist".Naunyn-Schmiedeberg's Archives of Pharmacology.343 (6):588–594.doi:10.1007/BF00184289.PMID1682817.
^Seyfried CA, Fuxe K, Wolf HP, Agnati LF (1982). "Demonstration of a new type of dopamine receptor agonist: An indolyl-3-butylamine. Actions at intact versus supersensitive dopamine receptors in the rat forebrain".Acta Physiologica Scandinavica.116 (4):465–468.doi:10.1111/j.1748-1716.1982.tb07168.x.PMID7171006.
