Activators of potassium M currents have anticonvulsant actions in two rat models of encephalitis

• Published in: European journal of pharmacology 2007-01, Vol.555 (1), p.23-29
• Main Authors: Solbrig, Marylou V., Adrian, Russell, Wechsler, Steven L., Koob, George F.
• Format: Article
• Language: English
• Subjects: Aminopyridines - pharmacology; Analgesics - pharmacology; Animals; Anticonvulsants - pharmacology; Biological and medical sciences; Borna; Borna Disease - drug therapy; Encephalitis, Viral - drug therapy; Encephalitis, Viral - physiopathology; Epilepsy; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Herpes; Herpes Simplex - drug therapy; Herpesvirus 1, Human; Human viral diseases; Infectious diseases; Male; Medical sciences; Naloxone; Naltrexone - analogs & derivatives; Naltrexone - pharmacology; Narcotic Antagonists - pharmacology; Nervous system (semeiology, syndromes); Neurology; Opioid; Pharmacology. Drug treatments; Potassium - physiology; Rats; Rats, Inbred Lew; Receptors, Opioid, delta - antagonists & inhibitors; Seizure; Seizures - chemically induced; Seizures - prevention & control; Substance Withdrawal Syndrome - etiology; Substance Withdrawal Syndrome - prevention & control; Viral diseases; Viral diseases with cutaneous or mucosal lesions and viral diseases of the eye; Virus
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2006.10.025

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.