Modification of the anticonvulsant activity of 2-amino-5-phosphonovalerate by agents affecting different neurotransmitter systems.
The effects of atropine (5 mg/kg), baclofen (10 mg/kg), gamma-hydroxybutyrate (300 mg/kg), gamma-butyrolactone (100 mg/kg) and muscimol (1 mg/kg) upon the action of 2-amino-5-phosphonovalerate (APV; an antagonist at receptors for N-methyl-D-aspartate) on the threshold current for seizures induced by electroshock, were studied in mice. Neither APV, up to 100 mg/kg, nor the other agents produced any significant increase in the convulsive threshold when tested alone. Muscimol had no effect on the action of APV (50 and 100 mg/kg) and the combination of APV with the subthreshold doses of atropine, baclofen, gamma-hydroxybutyrate and gamma-butyrolactone resulted in a clearcut anticonvulsant action. The observed increases in the threshold may be due to the suppressant effects of the drugs upon excitatory transmission, which eventually leads to the potentiation of the action of APV, resulting from blockade of N-methyl-D-aspartate receptors.
Czuczwar
S J
SJ
Turski
L
L
Chmielewska
B
B
Turski
W A
WA
Kleinrok
Z
Z
D015763:2-Amino-5-phosphonovalerate; D015107:4-Butyrolactone / Q000008:administration & dosage; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage*; D001285:Atropine / Q000008:administration & dosage; D001418:Baclofen / Q000008:administration & dosage; D001921:Brain / Q000187:drug effects*; D004347:Drug Interactions; D008297:Male; D051379:Mice; D009118:Muscimol / Q000008:administration & dosage; D018377:Neurotransmitter Agents / Q000502:physiology*; D012978:Sodium Oxybate / Q000008:administration & dosage; D009435:Synaptic Transmission / Q000187:drug effects; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives*
D000927:Anticonvulsants; D018377:Neurotransmitter Agents; D009118:Muscimol; D015763:2-Amino-5-phosphonovalerate; D001285:Atropine; D012978:Sodium Oxybate; D001418:Baclofen; D014633:Valine; D015107:4-Butyrolactone