Prolonged anticonvulsant action of glutamate metabotropic receptor agonists in inferior colliculus of genetically epilepsy-prone rats.
The anticonvulsant activity of (S)-4-carboxy-3-hydroxyphenylglycine ((S)-4C3HPG) (an antagonist of Group I and an agonist of Group II metabotropic glutamate (mGlu) receptors), of (1S,3S)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3S)-ACPD) (an agonist of Group II mGlu receptors), and of L-serine-O-phosphate (an agonist of Group III mGlu receptors) was studied against sound-induced seizures in genetically epilepsy-prone (GEP) rats following bilateral microinjection into the inferior colliculus. All 3 drugs produce dose-dependent suppression of all phases of sound-induced seizures (wild running, clonic and tonic). (S)-4C3HPG produces an immediate and short-lasting (< 2 h) protection against sound-induced seizures with an ED50 value of 4.3 (3.2-5.7) nmol, at 5 min. The preferential agonists of Group II and Group III mGlu receptors produce an immediate, transient (< 10 min) proconvulsant effect followed by a prolonged (> 1 day) anticonvulsant effect against sound-induced seizures. The anticonvulsant ED50 value for (1S,3S)-ACPD is 9 (5-18) nmol at 2 h, and for L-serine-O-phosphate is 36 (6.5-199) nmol at 2 days. It is concluded that mGlu receptor activation potently modifies seizure threshold.
Tang
E
E
Department of Clinical Neurosciences, Institute of Psychiatry, London, UK.
Yip
P K
PK
Chapman
A G
AG
Jane
D E
DE
Meldrum
B S
BS
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007245:Inferior Colliculi / Q000187:drug effects; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009622:Noise; D010768:Phosphoserine / Q000494:pharmacology*; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000037:antagonists & inhibitors
D018696:Neuroprotective Agents; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C078245:4-carboxy-3-hydroxyphenylglycine; D010768:Phosphoserine; D005998:Glycine