Mechanism of Action

Ketamine is chemically similar to PCP but has important differences (Jansen, 1990). Ketamine binds to the NMDA receptor complex on the same site as PCP, located inside the calcium channel. It works by inhibiting several of the excitatory amino acid neurotransmitters (Cotman & Monaghan, 1987; Hampton et al., 1982). Ketamine works globally, affecting numerous neurotransmitter systems, but its action, as an NMDA antagonist, is likely the cause of its schizotypal and dissociative symptoms. NMDA blockade causes an increase in dopamine release in the midbrain and prefrontal cortex as well

(Bubser Keseberg, Notz, & Griffiths, 1992), and this is likely the cause of its ability to reinforce and cause dependence. Furthermore, persisting memory deficits have been demonstrated (Curran & Monaghan, 2001).

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