Efficacy of moclobemide in a rat model of neurotoxicant-induced edema.
The potent antidepressant effect of moclobemide, a selective and reversible type A monoamine oxidase (MAO) inhibitor, is clinically established. In view of the ongoing debate on the neuroprotective properties of MAO inhibitors, the present study was undertaken to further define the protective effect of moclobemide in a rat model of neurotoxicant-induced edema. In this model, daily oral triethyltin (TET) administration for 5 consecutive days strongly perturbed the rat behaviour and induced a cerebral edema at the 5th day. Oral coadministration of moclobemide (2 x 100 mg.kg-1.day-1) with TET blocked the development of brain edema and the increase in the cerebral chloride content induced by TET. Moreover, moclobemide reduced the increase in the cerebral sodium content and attenuated the neurological deficit. In conclusion, moclobemide possesses potent protective properties in this rat model of cerebral edema, suggesting potential clinical utility as a neuroprotectant.
Girard
Philippe
P
Biocodex, Service de Pharmacologie, Zac de Mercières 60200 Compiègne, France. p.girard@biocodex.fr
Verniers
Danielle
D
Pansart
Yannick
Y
Gillardin
Jean-Marie
JM
D000284:Administration, Oral; D000818:Animals; D015992:Body Mass Index; D001929:Brain Edema / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D002118:Calcium / Q000378:metabolism; D002540:Cerebral Cortex / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D002712:Chlorides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007441:Intubation, Gastrointestinal; D008297:Male; D020912:Moclobemide / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008995:Monoamine Oxidase / Q000187:drug effects; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D009043:Motor Activity / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D014267:Triethyltin Compounds / Q000008:administration & dosage / Q000633:toxicity*; D014867:Water / Q000378:metabolism
D002712:Chlorides; D008996:Monoamine Oxidase Inhibitors; D014267:Triethyltin Compounds; D014867:Water; D012964:Sodium; D008995:Monoamine Oxidase; D020912:Moclobemide; D011188:Potassium; D002118:Calcium; C026405:bromotriethylstannane