title: Carisoprodol tolerance and precipitated withdrawal.
abstract: OBJECTIVE
  Carisoprodol is a muscle relaxant that acts at the GABA(A) receptor. Concerns about the abuse liability of carisoprodol are increasing, but evidence that carisoprodol produces tolerance and a significant withdrawal syndrome has yet to be established. The purpose of the current study was to determine if repeated administration of carisoprodol produces tolerance and withdrawal signs in a mouse model.
  
  
  METHODS
  Carisoprodol (0, 100, 200, 300, or 500 mg/kg bid, i.p.) was administered to Swiss-Webster mice for 4 days and loss-of-righting reflex was measured 20-30 min following each administration. On the fourth day, bemegride (20 mg/kg), flumazenil (20 mg/kg), or vehicle was administered following carisoprodol and withdrawal signs were measured. Separate groups of mice receiving the same treatment regimen and dose range were tested for spontaneous withdrawal at 6, 12 and 24 h after the last dose of carisoprodol.
  
  
  RESULTS
  The righting reflex was dose-dependently impaired following the first administration of carisoprodol. A 75-100% decrease in the magnitude of the impairment occurred over the four days of exposure, indicating the development of tolerance to the carisoprodol-elicited loss-of-righting reflex. Withdrawal signs were not observed within 24h following spontaneous withdrawal; however, bemegride and flumazenil each precipitated withdrawal within 15-30 min of administration.
  
  
  CONCLUSIONS
  Carisoprodol treatment resulted in tolerance and antagonist-precipitated withdrawal, suggesting it may have an addiction potential similar to that of other long-acting benzodiazepine or barbiturate compounds.
authors: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107-2699, USA. michael.gatch@unthsc.edu
authors: Michael B
authors: MB
authors: Gatch
authors: Jacques D
authors: JD
authors: Nguyen
authors: Theresa
authors: T
authors: Carbonaro
authors: Michael J
authors: MJ
authors: Forster
mesh_terms: D000818:Animals; D001534:Bemegride / Q000494:pharmacology; D002328:Carisoprodol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005442:Flumazenil / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D008297:Male; D051379:Mice; D009125:Muscle Relaxants, Central / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010812:Physical Stimulation; D011187:Posture; D013216:Reflex, Startle / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000523:psychology*; D014202:Tremor / Q000209:etiology / Q000523:psychology
chemical_list: D000697:Central Nervous System Stimulants; D018757:GABA Modulators; D009125:Muscle Relaxants, Central; D002328:Carisoprodol; D005442:Flumazenil; D001534:Bemegride