title: Intravenous dextromethorphan/quinidine inhibits activity of dura-sensitive spinal trigeminal neurons in rats.
abstract: BACKGROUND
  Migraine is a chronic neurological disorder characterized by episodes of throbbing headaches. Practically all medications currently used in migraine prophylaxis have a number of substantial disadvantages and use limitations. Therefore, the further search for principally new prophylactic antimigraine agents remains an important task. The objective of our study was to evaluate the effects of a fixed combination of dextromethorphan hydrobromide and quinidine sulphate (DM/Q) on activity of the spinal trigeminal neurons in an electrophysiological model of trigemino-durovascular nociception.
  
  
  METHODS
  The study was performed in 15 male Wistar rats, which were anaesthetized with urethane/α-chloralose and paralysed using pipecuronium bromide. The effects of cumulative intravenous infusions of DM/Q (three steps performed 30 min apart, 15/7.5 mg/kg of DM/Q in 0.5 mL of isotonic saline per step) on ongoing and dural electrical stimulation-induced neuronal activities were tested in a group of eight rats over 90 min. Other seven animals received cumulative infusion of equal volumes of saline and served as control.
  
  
  RESULTS
  Cumulative administration of DM/Q produced steady suppression of both the ongoing activity of the spinal trigeminal neurons and their responses to electrical stimulation of the dura mater.
  
  
  CONCLUSIONS
  It is evident that the observed DM/Q-induced suppression of trigeminal neuron excitability can lead to a reduction in nociceptive transmission from meninges to higher centres of the brain. Since the same mechanism is believed to underlie the pharmacodynamics of many well-known antimigraine drugs, results of the present study enable us to anticipate the potential efficacy of DM/Q in migraine.
authors.affiliation: Department of Neuropharmacology, Valdman Institute of Pharmacology, First St. Petersburg Pavlov State Medical University, Russia.|Laboratory of Cortico-Visceral Physiology, Pavlov Institute of Physiology, Russian Academy of Sciences, St. Petersburg, Russia.
authors.forename: A Y
authors.initials: AY
authors.lastname: Sokolov
authors.affiliation: Department of Neuropharmacology, Valdman Institute of Pharmacology, First St. Petersburg Pavlov State Medical University, Russia.|Laboratory of Cortico-Visceral Physiology, Pavlov Institute of Physiology, Russian Academy of Sciences, St. Petersburg, Russia.
authors.forename: O A
authors.initials: OA
authors.lastname: Lyubashina
authors.affiliation: Keck School of Medicine, Department of Neurology, University of Southern California, Los Angeles, USA.
authors.forename: R R
authors.initials: RR
authors.lastname: Berkovich
authors.affiliation: Department of Neuropharmacology, Valdman Institute of Pharmacology, First St. Petersburg Pavlov State Medical University, Russia.|Laboratory of Cortico-Visceral Physiology, Pavlov Institute of Physiology, Russian Academy of Sciences, St. Petersburg, Russia.
authors.forename: S S
authors.initials: SS
authors.lastname: Panteleev
mesh_terms: D000818:Animals; D003915:Dextromethorphan / Q000008:administration & dosage / Q000494:pharmacology*; D004388:Dura Mater; D004558:Electric Stimulation; D007262:Infusions, Intravenous; D008297:Male; D009474:Neurons / Q000187:drug effects*; D059225:Nociception / Q000187:drug effects; D011802:Quinidine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects; D014276:Trigeminal Nerve / Q000166:cytology / Q000187:drug effects*
chemical_list: D003915:Dextromethorphan; D011802:Quinidine