Vasoconstriction of porcine left anterior descending coronary artery by ecstasy and cathinone is not an indirect sympathomimetic effect.
3,4-methylenedioxymethamphetamine ('Ecstasy', MDMA) and cathinone, the active constituent of khat leaves, were examined on pig isolated left anterior descending coronary arteries to determine whether they cause vasoconstriction and whether this was an indirect sympathomimetic action. Coronary artery rings were set up in Krebs solution (37 degrees C) gassed with 5% CO2 in O2. Endothelium remained intact as indicated by relaxation by bradykinin. Isometric tension was recorded and cumulative concentration-response curves (CRCs) for noradrenaline, ecstasy or cathinone plotted as a percent of the constriction to KCl (60 mM). Noradrenaline-induced contractions of the coronary artery were enhanced by propranolol (1 microM) indicating beta-adrenoceptor-mediated opposing vasodilatation. Cocaine (10 microM) further potentiated, while prazosin (1 microM) virtually abolished the contractions to noradrenaline. Cathinone and ecstasy constricted the coronary artery rings, the peak contractions being 56.5+/-4.2% (n=4) and 37.3+/-2.4% (n=4), respectively. Higher concentrations relaxed. The vasoconstriction was not affected by cocaine (10 microM), prazosin (1 microM, in the presence of cocaine) or removal of the endothelium. There was no tachyphylaxis or desensitisation on repeated administration of single doses. Ecstasy- and cathinone-induced coronary vasoconstriction is therefore via mechanisms other than indirect sympathomimetic activity or alpha1 -adrenoceptors. This activity could explain the cardiac adverse effects following their excessive use.
Baker
Kathryn E
KE
Division of Pharmacology, Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK.
Herbert
Amy A
AA
Broadley
Kenneth J
KJ
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D013552:Swine; D013566:Sympathomimetics / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D000470:Alkaloids; D013566:Sympathomimetics; C023665:cathinone; D003042:Cocaine; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D009638:Norepinephrine; D011224:Prazosin