At which 'sigma' site are the spinal actions of ketamine mediated?
Electrophysiological experiments have been performed on rat spinal nociceptive reflexes to examine whether the spinal actions of ketamine are mediated at the haloperidol-sensitive sigma-site (which is particularly concentrated in the spinal ventral horn) or at the other site which has been referred to as sigma and which is characterized by phencyclidine (PCP), an antagonist of N-methylaspartate (NMA). The effects of ketamine on nociceptive reflexes were not affected by haloperidol 1-100 micrograms/kg i.v. The anticonvulsive agent MK-801, which is active at the PCP site but relatively inactive at the haloperidol-sensitive sigma-site, behaved like ketamine in reducing nociceptive reflexes at NMA-blocking doses; its actions were not affected by haloperidol at up to 1 mg/kg. Ketamine thus appears to manifest its spinal actions at the PCP site, a finding supportive of these spinal nociceptive reflexes being mediated by NMA receptors.
Parsons
C G
CG
Department of Physiology, Medical School, Bristol, U.K.
Gibbens
H
H
Magnago
T S
TS
Headley
P M
PM
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001667:Binding, Competitive; D003986:Dibenzocycloheptenes / Q000494:pharmacology; D016291:Dizocilpine Maleate; D006220:Haloperidol / Q000494:pharmacology; D007649:Ketamine / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010622:Phencyclidine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D017480:Receptors, sigma; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology
D003986:Dibenzocycloheptenes; D011957:Receptors, Opioid; D017480:Receptors, sigma; D007649:Ketamine; D016291:Dizocilpine Maleate; D010622:Phencyclidine; D006220:Haloperidol