3,4-methylenedioxymethamphetamine (‘Ecstasy’) is a recreational drug, the use of which has lead to a number of fatalities attributed to acute myocardial infarction (Dowling et al., 1987). Cathinone is the active constituent of khat (Catha edulis Forsk.) leaves, which are chewed for their central stimulant activity. Khat chewing is also linked to an increased risk of myocardial infarction (Al-Motarreb et al., 2002). Ecstasy (Fitzgerald & Reid, 1994) and cathinone (Kalix, 1992) are classified as indirectly acting sympathomimetic amines (ISA). This study investigates their actions on porcine isolated coronary vessels and whether they can be attributed to ISA.

Hearts from adult pigs of either sex were transported from the abattoir on ice. Left anterior decending coronary arteries were dissected from the ventricular surface and 5 mm rings suspended between wires in an organ bath. After 1 h equilibration under 1 g tension, cumulative concentration-response curves (CRCs) to ecstasy (3-300 µM), cathinone (3-300 µM) or noradrenaline (0.3-100 µM) were obtained in the absence or presence of i) the uptake inhibitor cocaine (10 µM), ii) cocaine plus the ₁-antagonist prazosin (1 µM), iii) propranolol (1 µM), iv) propranolol plus cocaine (1 µM), or v) propranolol plus prazosin (1 µM). Contractions were recorded on a PowerLab/4SP computer system and plotted as % of the contraction to 60 mM KCl added at the end.

Ecstacy and cathinone caused concentration-dependent contraction of pig coronary arteries. At the highest doses employed (300 µM), ecstacy and cathinone caused 61.9±13.9 (n=4) and 14.3±2.9% (n=6) of the KCl-induced contraction.

The CRC for the vasoconstriction by noradrenaline was potentiated by propranolol, at the maximum (1 mM) from 21.6±3.3 (n=4) to 33.6±5.5% (n=7), which failed to reach significance. Cocaine with propranolol further potentiated noradrenaline to 50.0±7.7% (n=6) (P<0.05), indicating that cocaine had inhibited neuronal uptake. Propranolol and prazosin virtually abolished the responses to noradrenaline, the contraction to the highest dose (1 mM) was only 3.6±1.8% (n=7), indicating substantial ₁-blockade.

In contrast, ecstasy and cathinone were unaffected by cocaine and prazosin. The contractions to the maximum concentrations of ecstasy and cathinone used (300 µM) in the presence of cocaine (71.0±9.1%, n=4 and 16.5±4.6%, n=6, respectively) and prazosin plus cocaine (69.8±10.7%, n=4 and 11.3±5.4%, n=6, respectively) were not significantly different (P >0.05) from that in their absence.

Therefore contractions of pig coronary arteries by cathinone and ecstasy are not due to indirect or direct sympathomimetic activity but to an as yet unidentified mechanism. This coronary vasoconstriction may be a causative factor in precipitating myocardial infarction after ecstasy and khat overuse.

Dowling, G.P., et al. (1987). J.A.M.A. 257, 1615-1617
Fitzgerald, J.L. & Reid, J.J. (1994). J. Pharm. Pharmacol., 46, 826-832
Kalix, P. (1992). Pharmacol. Toxicol.70, 77-86
Al-Motarreb, A., et al., (2002). Heart, 87, 279-280

Supported by the British Heart Foundation