Methcathinone intoxication in the rat: abrogation by dextrorphan.
OBJECTIVE
Methcathinone, a designer drug, has high abuse liability. In this study we characterized acute methcathinone toxicity in rats, attempting to determine whether the excitatory amino acid receptor antagonist dextrorphan can antagonize methcathinone intoxication.


METHODS
Intoxication was produced with IV methcathinone infusion (5 mg/kg/minute; 100 mg/mL) in conscious rats. We studied pretreatment, in which dextrorphan or vehicle was injected 30 minutes before methcathinone infusion. In a second protocol, dextrorphan or saline solution was given immediately after the onset of convulsions.


RESULTS
Methcathinone caused tachycardia (maximal increase, 131 +/- 10 beats/minute), hyperthermia (+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) significantly reduced hyperthermia (+.1 degree +/- .3 degree C) and tachycardia and increased the convulsive (dextrorphan, 134 +/- 9 mg/kg; vehicle, 67 +/- 4 mg/kg) and lethal doses (dextrorphan, 204 +/- 9 mg/kg; vehicle, 160 +/- 5 mg/kg). Dextrorphan, given immediately after the initial methcathinone convulsion, reduced hyperthermic and tachycardic responses but not the lethality of methcathinone.


CONCLUSIONS
Blockade of excitatory amino acid receptors by dextrorphan minimizes acute methcathinone intoxication.
Rockhold
R W
RW
Department of Emergency Medicine, University of Mississippi Medical Center, Jackson.
Carlton
F B
FB
Corkern
R
R
Derouen
L
L
Bennett
J G
JG
Hume
A S
AS
D000818:Animals; D015198:Designer Drugs / Q000633:toxicity*; D003917:Dextrorphan / Q000008:administration & dosage / Q000494:pharmacology*; D005334:Fever / Q000139:chemically induced; D007928:Lethal Dose 50; D008297:Male; D011427:Propiophenones / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017459:Receptors, Amino Acid / Q000037:antagonists & inhibitors; D012640:Seizures / Q000139:chemically induced*; D013610:Tachycardia / Q000139:chemically induced; D013997:Time Factors
D015198:Designer Drugs; D011427:Propiophenones; D017459:Receptors, Amino Acid; D003917:Dextrorphan; C047806:monomethylpropion