Discovered in 1926, phencyclidine is a hallucinogen that remained without significant utility until 30 years later when its potential to reduce or even eliminate pain was demonstrated in animal models. Briefly used as an analgesic-amnesic anesthetic, it was later abandoned due to high incidence of bizarre psychiatric effects such as delirium, agitation, disorientation, and hallucination (Abraham et al. 1996). Ketamine, a PCP derivative, is a well-known sedative, anesthetic, amnesic, and analgesic. PCP and similar compounds produce a dissociative phenomenon, in which the subject has an "out of body" experience. When taken orally, the effects develop in 1-2 h and last for about 10 h. Their mechanism of action is complex and includes agonist, partial agonist, and antagonist effects at various adrenergic, dopaminergic, and serotonin receptors (Abraham et al. 1996). Sympathetic activation, hallucination, delirium, amnesia, depression and, long-term memory and cognitive dysfunction are some of the common side effects. In high doses, respiratory arrest can occur. Alternatively, this class of drugs has the ability to antagonize N-methyl-D-aspartate (NMDA) receptors which has clinical implication in chronic pain. Activation of NMDA receptors causes the spinal cord neuron to become more responsive to all of its inputs, resulting in central sensitization. NMDA receptor activation not only increases the cell's response to pain stimuli but also decreases neuronal sensitivity to opioid receptor agonists.
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