title: Activators of potassium M currents have anticonvulsant actions in two rat models of encephalitis.
abstract: Opioid systems in hippocampus regulate excitability and kappa opioids have a role in anticonvulsant protection, but their mechanisms of action are incompletely understood. We examined the ability of opioid and nonopioid agents with overlapping ionic mechanisms and actions similar to kappa opioid agonists, to block seizures in rat models of encephalitis due to Borna Disease virus and Herpes Simplex Virus Type-1. Naltrindole, a delta antagonist and thus a kappa opioid sparing agent, (10 mg/kg s.c.) blocked spontaneous and naloxone (opioid antagonist)-induced seizures in the models, but produced somatic signs similar to opioid withdrawal. Given that delta antagonists as well as kappa opioid agonists in hippocampus enhance potassium M currents (I(M)), we tested the effect of the I(M) augmenter flupirtine. Flupirtine (20 mg/kg i.p.) prevented seizures in Borna and herpes infected rats, without signs of withdrawal, hypotonia or sedation. The results support the efficacy of opioid and nonopioid drugs in modulating naloxone-induced seizures in critical illness due to viral encephalitis and by analogy, opioid withdrawal seizures.
authors.affiliation: Department of Neurology, University of California-Irvine, Irvine, California 92697-4292 USA. msolbrig@uci.edu
authors.forename: Marylou V
authors.initials: MV
authors.lastname: Solbrig
authors.forename: Russell
authors.initials: R
authors.lastname: Adrian
authors.forename: Steven L
authors.initials: SL
authors.lastname: Wechsler
authors.forename: George F
authors.initials: GF
authors.lastname: Koob
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001890:Borna Disease / Q000188:drug therapy; D018792:Encephalitis, Viral / Q000188:drug therapy* / Q000503:physiopathology; D006561:Herpes Simplex / Q000188:drug therapy; D018259:Herpesvirus 1, Human; D008297:Male; D009270:Naloxone; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D011188:Potassium / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D013375:Substance Withdrawal Syndrome / Q000209:etiology / Q000517:prevention & control
chemical_list: D000631:Aminopyridines; D000700:Analgesics; D000927:Anticonvulsants; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D009270:Naloxone; D009271:Naltrexone; C055382:naltrindole; C034161:flupirtine; D011188:Potassium