The dose-response relationship and therapeutic window for dizocilpine (MK-801) in a rat focal ischaemia model.
The purpose of the present study was to examine the dose-response relationship and the maximum time for which effective therapy could be delayed for the N-methyl-D-aspartate antagonist dizocilpine (MK-801) as a neuroprotective agent in a permanent focal ischaemia model in the rat. The ED50 for dizocilpine in the amelioration of cortical damage in this model was found to be approximately 0.3 mg/kg (single i.p. dose, 30 min post onset of ischaemia) and significant protection was only obtained when therapy (3 mg/kg i.p.) was delayed for one hour or less after the onset of ischaemia. In a further experiment, dizocilpine 3 mg/kg i.p., produced a peak plasma level of 44 ng/ml and had a t1/2 elimination of 1.65 h.
Hatfield
R H
RH
Merck, Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
Gill
R
R
Brazell
C
C
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D002546:Ischemic Attack, Transient / Q000188:drug therapy*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D016291:Dizocilpine Maleate