Distinct features of seizures induced by cocaine and amphetamine analogs

Eur J Pharmacol. 1999 Jul 21;377(2-3):167-73. doi: 10.1016/s0014-2999(99)00419-7.

Abstract

Seizure-related emergencies caused by stimulants of abuse have been increasing. To better understand the nature of these drug-induced convulsions, we characterized the seizure patterns associated with high doses of cocaine, and the amphetamine analogs, methamphetamine, methylenedioxymethamphetamine (MDMA) and 4-methylaminorex. The features of the stimulant-induced seizures were distinct and included the following: (1) the duration of convulsive activity was shortest for cocaine and longest for methamphetamine, (2) only MDMA produced a secondary clonic phase after the initial ictal event, and (3) 4-methylaminorex manifested a very steep dose-response curve. Differential preventive profiles of anticonvulsant agents on the stimulant-induced seizures also were observed. For example, cocaine-related seizures were most effectively prevented by, while methamphetamine-induced seizures were completely refractory to, phenytoin pretreatment. The only anticonvulsants which appeared to influence methamphetamine-related convulsions were diazepam and valproate. A unique feature of 4-methylaminorex was that related seizures were almost completely blocked by the calcium channel blocker, flunarizine.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Central Nervous System Agents / toxicity*
  • Central Nervous System Stimulants / toxicity
  • Diazepam / pharmacology
  • Dose-Response Relationship, Drug
  • Flunarizine / pharmacology
  • Hallucinogens / toxicity
  • Male
  • Methamphetamine / toxicity*
  • Mice
  • N-Methyl-3,4-methylenedioxyamphetamine / toxicity*
  • Oxazoles / toxicity*
  • Rats
  • Rats, Sprague-Dawley
  • Seizures / chemically induced
  • Seizures / prevention & control*
  • Time Factors
  • Valproic Acid / pharmacology

Substances

  • Central Nervous System Agents
  • Central Nervous System Stimulants
  • Hallucinogens
  • Oxazoles
  • Methamphetamine
  • Valproic Acid
  • 4-methylaminorex
  • N-Methyl-3,4-methylenedioxyamphetamine
  • Diazepam
  • Flunarizine