Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Clonidine, an alpha-2 adrenergic agonist, induced in rats a synchronization of the electrical activity of the brain (EEG) accompanied by sedation starting from the dose of 0.05 mg/kg, i.p. 2. This drug (0.05 mg/kg, i.p.) was also able to influence both the EEG and behavioural effects elicited by two "dissociative anaesthetics", PCP and KT. 3. At low and moderate doses of these two drugs, clonidine fully inhibited the EEG and behavioural effects, whereas at high doses of both drugs clonidine potentiated these effects. 4. Yohimbine was able to revert the inhibitory and potentiating effects produced by clonidine. It was also able to revert sedation accompanied by EEG synchronization. 5. Prazosin, on the other hand, was not able to produce such effects. This fact suggests that the alpha-2 adrenoceptors are involved in these effects. 6. Based on our findings, the interaction of the dissociative anaesthetics (PCP-KT) with the central adrenergic receptors seems to be very complex. The possible relevance of clonidine on both the improvement of KT-induced anaesthesia and the treatment of PCP-intoxication is also discussed.
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PMID:An EEG and behavioural study on the interactions of clonidine with phencyclidine and ketamine in rats. 230 39

The noncompetitive NMDA receptor antagonist phencyclidine (PCP) and the neuronal cannabinoid receptor agonist delta9-tetrahydrocannabinol (THC) are two agents shown to have psychotomimetic properties in humans. Both drugs increase dopamine release and utilization in the prefrontal cortex, a brain region thought to be dysfunctional in schizophrenia. In the present series of studies, the effects of drugs acting at alpha-noradrenergic receptors on PCP- and THC-induced increases in prefrontal cortical and nucleus accumbens dopamine utilization in the rat were examined. Clonidine, an alpha2 noradrenergic receptor agonist, completely blocked the activation of mesoprefrontal dopamine system by THC or PCP. In addition, the alpha1 noradrenergic receptor antagonist prazosin blocked the PCP-induced increase in prefrontal cortical dopamine utilization. These data may provide new insights concerning pharmacological therapies for acute drug-induced psychoses and behavioral abnormalities in human PCP and THC abusers.
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PMID:Alpha-noradrenergic receptor modulation of the phencyclidine- and delta9-tetrahydrocannabinol-induced increases in dopamine utilization in rat prefrontal cortex. 941 14

N-methyl-D-aspartic acid/glutamate receptor antagonists induce psychotomimetic effects in humans and animals, and much research has focused on the neurochemical and network-level effects that mediate those behavioral changes. For example, a reduction in NMDA-dependent glutamatergic transmission triggers increased release of the monoamine transmitters, and some of these changes are implicated in the cognitive, behavioral and neuroanatomical effects of phencyclidine (PCP). Alpha-2 adrenoceptor agonists (e.g., clonidine) are effective at preventing many of the behavioral, neurochemical and anatomical effects of NMDA antagonists. Evidence has indicated that a key mechanism of the clonidine-induced reversal of the effects of NMDA antagonists is an attenuation of enhanced dopamine release. We have pursued these findings by investigating the effects of alpha-2 agonists on PCP-evoked dopamine efflux in the prefrontal cortex of freely moving rats. Clonidine (0.003-0.1 mg/kg, i.p.) dose-dependently attenuated the ability of PCP (2.5 mg/kg, i.p.) to increase cortical dopamine output. The effects of clonidine were prevented by the alpha-2A subtype selective antagonist BRL-44408 (1 mg/kg, i.p.). Guanfacine, which is an alpha-2 agonist with a higher affinity for the 2A, compared with 2B or 2C, subtypes, also blocked the ability of PCP to increase dopamine efflux in the prefrontal cortex. These data indicate that alpha-2A agonists are effective at counteracting the hyperdopaminergic state induced by PCP and may play a role in their neurobehavioral effects in this putative animal model for schizophrenia.
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PMID:Clonidine and guanfacine attenuate phencyclidine-induced dopamine overflow in rat prefrontal cortex: mediating influence of the alpha-2A adrenoceptor subtype. 1897 8