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Phencyclidine
- Dissociative anaesthetic
- Parke Davis 1950
- Withdrawn from human use in 1965
- Related to Ketamine
- Illicit use
- San Francisco 1967
- Cheap, distributed by crips
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Low dose effects
Alcohol-like effect
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Moderate dose effects
- Distortion of space and time, psychotic reactions
- Anaesthetic and analgesic
- Blank stare, amnesia, mutism
-
High dose effects
- Model of acute schizophrenia
- Last up to 1-7 days
- Sometimes violent, abusive behavior
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Overdose
Respiratory depression/seizures
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Reinforcing effects
- Readily self-adminstered in animals
- To point of intoxication
- Modest tolerance
- Addiction and withdrawal
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2 distinct binding sites
- Sigma site -> generalizes with benzomorphans
- PCP site -> part of NMDA receptor
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Glutamate
- ubiquitous excitatory transmitter
- depolarizes virtually all cells
- primary transmitter for fast excitatory signaling
-
Glutamate receptors
- Ionotropic
- Non-NDMA -> AMPA and Kainate
- NDMA -> selective binds N-methyl-D-aspartate
- Metabotropic
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PCP/NMDA interaction
- Noncompetitive antagonist at NMDA receptor
- site inside channel -> block channel
- Does not antagonize AMPA/kainate effect
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Glutamate excitotoxicity
- too much glutamate kills the cell
- MK-801
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