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Neuromodulatory role of serotonin in the anticonvulsant activity of 2-phenylbenzoate of 3-diethylamino-1-propanol.HCl (JAW-669).

Abstract
The role of serotonin in the mediation of the anticonvulsant activity of JAW-669 was investigated against maximal electric shock (MES)-induced seizures in mice. A dose-dependent protection against seizures was provided by JAW-669 (4, 6 and 8 mg/kg, IP) and the calculated ED50 value was 6.01 mg/kg, IP. Pretreatment of mice with 5-hydroxytryptophan (50 mg/kg, IP) 2 hr before the administration of JAW-669 (6.01 mg/kg, IP) was found to cause a 40% increase in the ability of JAW-669 to provide protection against MES-induced seizures. Similar pretreatment with tryptophan (100 mg/kg, IP, 1 hr) caused a 30% decrease in the anticonvulsant activity of JAW-669. Prior administration of p-chlorophenylalanine (300 mg/kg, IP, 48 hr) and methysergide (10 mg/kg, IP; 0.5 hr) before administration of JAW-699 caused a 66% and 74% decrease, respectively, in the ability of JAW-669 to provide protection against MES-induced seizures. These results suggest a facilitatory role of serotonin in the anticonvulsant activity of JAW-669.
AuthorsL M Leadbetter, S J Brumleve, J A Waters, S S Parmar
JournalPhysiology & behavior (Physiol Behav) Vol. 46 Issue 1 Pg. 35-7 (Jul 1989) ISSN: 0031-9384 [Print] United States
PMID2530601 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anticonvulsants
  • Biphenyl Compounds
  • Propanolamines
  • Receptors, Serotonin
  • 3-diethylamino-1-propanol 2-phenylbenzoate
  • Serotonin
  • Tryptophan
  • 5-Hydroxytryptophan
  • Fenclonine
  • Methysergide
Topics
  • 5-Hydroxytryptophan (pharmacology)
  • Animals
  • Anticonvulsants (pharmacology)
  • Biphenyl Compounds (pharmacology)
  • Brain (drug effects)
  • Dose-Response Relationship, Drug
  • Electroshock
  • Fenclonine (pharmacology)
  • Kindling, Neurologic (drug effects)
  • Male
  • Methysergide (pharmacology)
  • Mice
  • Mice, Inbred Strains
  • Propanolamines (pharmacology)
  • Receptors, Serotonin (drug effects)
  • Serotonin (physiology)
  • Tryptophan (pharmacology)

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