PD117302, a selective non-peptide opioid kappa agonist, protects against NMDA and maximal electroshock convulsions in rats.

Abstract

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.

• Authors: F C Tortella, L Robles, E Echevarria, J C Hunter, J Hughes
• Journal: Life sciences (Life Sci) Vol. 46 Issue 17 Pg. PL1-7 ( 1990) ISSN: 0024-3205 [Print] Netherlands
• PMID: 2160036 (Publication Type: Journal Article)

Chemical References

• Anticonvulsants
• Pyrroles
• Receptors, Opioid
• Receptors, Opioid, kappa
• Thiophenes
• PD 117302
• Aspartic Acid
• N-Methylaspartate
• Flurothyl

Topics

• Animals
• Anticonvulsants
• Aspartic Acid (analogs & derivatives, antagonists & inhibitors)
• Dose-Response Relationship, Drug
• Electroshock
• Flurothyl (antagonists & inhibitors)
• Male
• N-Methylaspartate
• Pyrroles (pharmacology)
• Random Allocation
• Rats
• Rats, Inbred Strains
• Receptors, Opioid (drug effects)
• Receptors, Opioid, kappa
• Thiophenes (pharmacology)
• Time Factors