J Korean Med Sci.  2002 Feb;17(1):96-102. 10.3346/jkms.2002.17.1.96.

Change of Hyperexcitability of Hippocampus by Cyclosporin A and Its Modulatory Action by Fentanyl

• Choi BJ
• Whang KT

• KMID: 2157602
• DOI: http://doi.org/10.3346/jkms.2002.17.1.96

Abstract

Cyclosporin A is used to treat patients with immune-mediated diseases, chronic diseases requiring organ transplantation, or malignancies. These conditions often require higher cyclosporin A doses, which may be toxic to the central nervous system. Fentanyl is also used in clinical conditions that have a risk of hypoxic neurosusceptiblity, which suggests that the drug may be a neuroprotective agonist against brain ischemic injury. Fentanyl is an opioid agonist and appears to play an important role in regulating the excitability of the hippocampus under electroconvulsion. In this study, the effects of fentanyl on modulating cyclosporin A-induced neurotoxicity was investigated. Treatment with 3 micrometer of cyclosporin A was found to reduce the electroconvulsive activity threshold. Fifty ng/mL of fentanyl reduced the electroconvulsive activity, and 1 micrometer of DAGO ([D-Ala2, N-Me-Phe4, Gly-ol]-enkephalin) also decreased the electroconvulsive activity. Fifty ng/mL of fentanyl was also found to reduce cyclosporin A-induced electroconvulsive activity. Although cyclosporin A neurotoxicity may be observed in various conditions, the opioid effect of neuroprotection may be involved in an interrelated mechanism. The exogenous opioid agonist suppressed cyclosporin A-induced electroconvulsive activity. Furthermore, there may be a functional anticonvulsant effect on cyclosporin A-induced neurotoxicity with an increased opioid agonist concentration.

Keyword

Neurotoxicity; Cyclosporin A; Fentanyl

MeSH Terms

Analgesics, Opioid/*pharmacology
Animals
Culture Techniques
Cyclosporine/*pharmacology
Dose-Response Relationship, Drug
Electrophysiology
Enkephalin, Ala(2)-MePhe(4)-Gly(5)-/pharmacology
Female
Fentanyl/*pharmacology
Hippocampus/*drug effects/physiopathology
Neuroprotective Agents/*agonists
Rats
Rats, Sprague-Dawley