Functional evidence for PCP-like effects of the anti-stroke candidate MK-801.
MK-801 is an indirect antagonist of the NMDA excitatory amino acid receptor which is being considered for possible clinical development for treatment of epilepsy and stroke. MK-801 was evaluated for its effects on regional brain energy metabolism by means of Sokoloff's 2-deoxyglucose (2-DG) autoradiography method. MK-801 produced dramatic alterations in regional energy metabolism, exciting Papez circuit and dopaminergic structures most intensely. The pattern of metabolic alterations was virtually indistinguishable from that previously described for the psychotomimetic drug of abuse, phencyclidine (PCP). It is concluded that MK-801 is at risk for possibly producing PCP-like psychotomimetic effects.
Piercey
M F
MF
CNS Research, Upjohn Company, Kalamazoo, MI 49001.
Hoffmann
W E
WE
Kaczkofsky
P
P
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001345:Autoradiography; D001921:Brain / Q000033:anatomy & histology; D002561:Cerebrovascular Disorders / Q000188:drug therapy*; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D016291:Dizocilpine Maleate; D004734:Energy Metabolism / Q000187:drug effects; D008297:Male; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D000927:Anticonvulsants; D003986:Dibenzocycloheptenes; D016291:Dizocilpine Maleate; D010622:Phencyclidine