Neuromodulatory role of serotonin in the anticonvulsant activity of 2-phenylbenzoate of 3-diethylamino-1-propanol.HCl (JAW-669).
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.
Leadbetter
L M
LM
Department of Physiology, University of North Dakota, School of Medicine, Grand Forks 58202.
Brumleve
S J
SJ
Waters
J A
JA
Parmar
S S
SS
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D010134:Fenclonine / Q000494:pharmacology; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D011412:Propanolamines / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000502:physiology*; D014364:Tryptophan / Q000494:pharmacology
D000927:Anticonvulsants; D001713:Biphenyl Compounds; D011412:Propanolamines; D011985:Receptors, Serotonin; C061717:3-diethylamino-1-propanol 2-phenylbenzoate; D012701:Serotonin; D014364:Tryptophan; D006916:5-Hydroxytryptophan; D010134:Fenclonine; D008784:Methysergide