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Serotonin as a facilitatory neurotransmitter in the anticonvulsant activity of methaqualone
1Department of Physiology, University of North Dakota, School of Medicine, Grand Forks 58202.
Abstract:
The neuromodulatory role of serotonin in the anticonvulsant activity of methaqualone was investigated. A dose-dependent increase in the ability of methaqualone to provide protection against pentylenetetrazol (90 mg/kg SC)-induced convulsions in mice was observed. The ED50 value for the anticonvulsant activity of methaqualone was calculated and found to be 60 mg/kg, IP. Pretreatment of mice with 5-hydroxytryptophan (100 mg/kg, IP, 2 hr) and p-chlorophenylalanine (300 mg/kg, IP, 2 hr), causing an increase in brain serotonin levels, resulted in a 60% and 80% increase, respectively, in the anticonvulsant activity of methaqualone. Similar pretreatment with p-chlorophenylalanine (300 mg/kg, IP, 48 hr), causing a lowering of brain serotonin, and methysergide (10 mg/kg, IP, 0.5 hr), causing blockade of brain serotonin receptors, resulted in a 40% and 20% decrease, respectively, in the ability of methaqualone to provide protection against pentylenetetrazol-induced convulsions. These results suggest a facilitatory role of serotonin in the anticonvulsant activity of methaqualone.
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