Abstract
BACKGROUND AND PURPOSE: 3,4-Methylenedioxypyrovalerone (MDPV) is a synthetic cathinone with stimulatory cardiovascular effects that can lead to serious medical complications. Here, we examined the pharmacological mechanisms underlying these cardiovascular actions of MDPV in conscious rats. EXPERIMENTAL APPROACH: Male Sprague-Dawley rats had telemetry transmitters surgically implanted for the measurement of BP and heart rate (HR). On test days, rats were placed individually in standard isolation cubicles. Following drug treatment, cardiovascular parameters were monitored for 3 h sessions. KEY RESULTS: Racemic MDPV (0.3-3.0 mg·kg(-1) ) increased BP and HR in a dose-dependent manner. The S(+) enantiomer (0.3-3.0 mg·kg(-1) ) of MDPV produced similar effects, while the R(-) enantiomer (0.3-3.0 mg·kg(-1) ) had no effects. Neither of the hydroxylated phase I metabolites of MDPV altered cardiovascular parameters significantly from baseline. Pretreatment with the ganglionic blocker chlorisondamine (1 and 3 mg·kg(-1) ) antagonized the increases in BP and HR produced by 1 mg·kg(-1) MDPV. The α(1) -adrenoceptor antagonist prazosin (0.3 mg·kg(-1) ) attenuated the increase in BP following MDPV, while the β-adrenoceptor antagonists propranolol (1 mg·kg(-1) ) and atenolol (1 and 3 mg·kg(-1) ) attenuated the HR increases. CONCLUSIONS AND IMPLICATIONS: The S(+) enantiomer appeared to mediate the cardiovascular effects of MDPV, while the metabolites of MDPV did not alter BP or HR significantly; MDPV increased BP and HR through activation of central sympathetic outflow. Mixed-action α/β-adrenoceptor antagonists may be useful as treatments in counteracting the adverse cardiovascular effects of MDPV.