Ketamine haloperidol

Both phencyclidine and ketamine bind with high affinity to a number of receptors in the brain, but it is now accepted that the primary target is the sigma-PCP receptor site located in the ion channel of the NMDA excitatory amino acid receptor complex. The precise function of this receptor in the brain is still the subject of debate. It is now known that there are two distinct sigma receptor sites in the mammalian brain (ctj and a2) which are not associated with the NMDA receptor complex. Haloperidol and the atypical neuroleptic remoxipride bind with high affinity to such sites, and it has been postulated that some typical and atypical neuroleptics may owe some of their pharmacological effects to their action on such receptors. 

Krystal JH, D Souza DC, Karper LP, Bennett A, Abi-Dargham A, et al. 1999. Interactive effects of subanesthetic ketamine and haloperidol in healthy humans. Psychopharmacology (Berl) 145 193-204. 

Oranje B, Gispen-de Wied CC, Verbaten MN, Kahn RS. 2002. Modulating sensory gating in healthy volunteers The effects of ketamine and haloperidol. Biol Psychiatry 52 ... 

The interaction of the dopamine antagonist haloperidol 5 mg orally with subanesthetic doses of ketamine has been studied in a placebo-controlled study in 20 healthy volunteers over 4 days (53). Haloperidol pretreatment reduced impairment of executive cognitive functions produced by ketamine and reduced the anxiogenic effects of ketamine. However, it failed to block the ability of ketamine to produce psychosis, perceptual changes, negative symptoms, or euphoria, and it increased the sedative and prolactin responses to ketamine. These results imply that ketamine may impair executive cognitive functions via dopamine receptor activation in the frontal cortex, but that the psychoactive effects of ketamine are not mediated via dopamine receptors, but rather via NMDA receptor antagonism. 

The hypoglutamatergic hypothesis of schizophrenia is attractive because it is consistent with the lack of changes in Da number in schizophrenia, and the increases in dopamine release in schizophrenia. They are also consistent with the ability of the noncompetitive NMDA antagonists PCP and ketamine to induce behaviors reminiscent of the positive symptoms of schizophrenia in normals and precipitate these episodes in patients. Ketamine was administered to schizophrenic patients acutely in a blinded, placebo-controlled trial (31). The drug caused a dose-related initiation of positive psychotic symptoms that were not blocked by haloperidol. The patients... 

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