PD117302, a selective non-peptide opioid kappa agonist, protects against NMDA and maximal electroshock convulsions in rats.
The pharmacological profile of PD117302 was studied in three rat models of experimental seizures. It was determined that PD117302 is a potent and efficacious anticonvulsant against NMDA (ED50 = 0.27 mg/kg, i.v.) and MES (ED50 = 16.3 mg/kg, s.c.), but not flurothyl, convulsions. Its anticonvulsant profile was dose- and time-dependent, stereospecific and sensitive to naloxone and the selective kappa opioid antagonist nor-binaltorphimine. Given these findings, we suggest that PD117302 acts via the kappa receptor to modulate seizure protection. Furthermore, in view of its marked ability to block NMDA excitotoxicity (including lethality) it seems possible that this drug, or related compounds, may have potential therapeutic utility as a neuroprotective agent.
Tortella
F C
FC
Department of Medical Neurosciences, Walter Reed Army Institute of Research, Washington, D.C. 20307-5100.
Robles
L
L
Echevarria
E
E
Hunter
J C
JC
Hughes
J
J
D000818:Animals; D000927:Anticonvulsants; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D005481:Flurothyl / Q000037:antagonists & inhibitors; D008297:Male; D016202:N-Methylaspartate; D011758:Pyrroles / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects; D017473:Receptors, Opioid, kappa; D013876:Thiophenes / Q000494:pharmacology*; D013997:Time Factors
D000927:Anticonvulsants; D011758:Pyrroles; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D013876:Thiophenes; C054718:PD 117302; D001224:Aspartic Acid; D016202:N-Methylaspartate; D005481:Flurothyl