METHCATHINONE INTOXICATION IN THE RAT - ABROGATION BY DEXTRORPHAN

Study objective: Methcathinone, a designer drug, has high abuse liabil ity. In this study we characterized acute methcathinone toxicity in ra ts, attempting to determine whether the excitatory amino acid receptor antagonist dextrorphan can antagonize methcathinone intoxication. Met hods: Intoxication was produced with IV methcathinone infusion (5 mg/k g/minute; 100 mg/mL) in conscious rats. We studied pretreatment, in wh ich dextrorphan or vehicle was injected 30 minutes before methcathinon e infusion. In a second protocol, dextrorphan or saline solution was g iven immediately after the onset of convulsions. Results: Methcathinon e caused tachycardia (maximal increase, 131 +/- 10 beats/minute), hype rthermia (+2.3 degrees C), convulsions, and cardiorespiratory collapse in vehicle-pretreated rats (n = 9). Death occurred after 32.0 +/- 1.1 minutes of infusion. Dextrorphan pretreatment (25 mg/kg; n = 7) signi ficantly reduced hyperthermia (+.1 degrees +/- .3 degrees C) and tachy cardia and increased the convulsive (dextrorphan, 134 +/- 9 mg/kg; veh icle, 67 +/- 4 mg/kg) and lethal doses (dextrorphan, 204 +/- 9 mg/kg; vehicle, 160 +/- 5 mg/kg). Dextrorphan, given immediately after the in itial methcathinone convulsion, reduced hyperthermic and tachycardic r esponses but not the lethality of methcathinone. Conclusion: Blockade of excitatory amino acid receptors by dextrorphan minimizes acute meth cathinone intoxication.