Anticonvulsant effect of cytoskeletal depolymerizers in combination with potassium channel opener and adenylate cyclase activator; a causative link with nerve growth factor?
Anticonvulsant effect of cytoskeletal depolymerizing drugs in combination with potassium channel (KATP) opener and adenylate cyclase activator was evaluated in animal models of epilepsy. Seizures were induced in the animals by subjecting them to maximal electroshock (MES) or by injecting a chemical convulsant, pentylenetetrazole (PTZ). Moreover a correlation with the nerve growth factor (NGF) was also investigated. The anticonvulsant effect of minoxidil (1200 micrograms/kg i.p.) and Deacetylforskolin (600 micrograms/kg i.p.) was significantly enhanced in the mice pre-treated with cytoskeletal depolymerizing drugs. On the other hand nerve growth factor potentiated the convulsive phenomenon and decreased the seizure threshold in both the electroshock and chemically induced convulsions. Another interesting feature was the interaction of cytochalasin B, a microfilament disrupter in preventing the action of mNGF and PTZ. This study demonstrates the importance of interaction between cytoskeletal structures and signalling molecules in determining the convulsive threshold. This study clearly points to the importance of the nerve growth factor in convulsive phenomenon.
Tyagi
M G
MG
Department of Pharmacology, Christian Medical College, Bagayam, Vellore 632 002.
Jose
V M
VM
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage*; D005576:Colforsin / Q000008:administration & dosage / Q000031:analogs & derivatives; D003571:Cytochalasin B / Q000008:administration & dosage; D003599:Cytoskeleton / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004827:Epilepsy / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D005260:Female; D008297:Male; D051379:Mice; D008914:Minoxidil / Q000008:administration & dosage; D020932:Nerve Growth Factor / Q000008:administration & dosage / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects; D015398:Signal Transduction
D000927:Anticonvulsants; D015221:Potassium Channels; D005576:Colforsin; D003571:Cytochalasin B; D008914:Minoxidil; D020932:Nerve Growth Factor; D000262:Adenylyl Cyclases