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)

The behavioral and biochemical effects of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 [+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate) were compared with those of phencyclidine (PCP). In the dose range used in this study, MK-801 (0.125-0.5 mg/kg i.p.) produced ataxia and other behavioral responses which were similar to PCP (5-10 mg/kg i.p.). However, turning and backpedalling induced by MK-801 were not dose-dependent and less intense at the dose producing approximately the same level of ataxia as PCP. Neurochemically, MK-801 (0.5 mg/kg i.p.) increased dopamine turnover in the cortex and striatum, but had no effect on 5-HT systems. It was also 3.4 times less potent in inhibiting 5-HT uptake than PCP. These results suggest that the behavioral responses induced by MK-801 involve primarily the PCP receptor and the dopamine system, and that the differences from PCP reflect a reduced effect on the 5-HT neuronal system.
 ...
PMID:Comparison of the behavioral and biochemical effects of the NMDA receptor antagonists, MK-801 and phencyclidine. 255 33

We have investigated whether metaphit, a derivative of phencyclidine (PCP) which irreversibly binds to a population of PCP receptor sites in rat brain, blocks PCP-induced head-twitch response which is produced through serotonin2 (5-HT2) receptors, and also whether metaphit decreases the capacity of 5-HT2 receptors. Metaphit (1 mumol/rat) had decreased the intensity of PCP-induced head-twitch response and had depleted both PCP and 5-HT2 receptors by 24 h after administration, but it failed to block 5-HT agonist 5-methoxy-N,N-dimethyltryptamine-induced 5-HT1A receptor-dependent behaviors. These results reconfirmed our hypothesis that PCP and 5-HT2 receptors may have very similar binding sites.
 ...
PMID:Effects of metaphit on phencyclidine and serotonin2 receptors. 255 11

The effects of phencyclidine (PCP) on the levels of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in discrete brain areas of mouse were investigated. Following a single administration, PCP significantly increased at 60 min the level of 5-HT but not 5-HIAA in the cortex. However, acute administration of PCP induced no changes of 5-HT and 5-HIAA levels in other brain areas investigated. On the other hand, chronic treatment of PCP produced a significant increase the striatal 5-HT and 5-HIAA levels by about 30% and 20%, respectively. These increased levels were gradually returned to the control levels, and there was no difference of these levels between the control group and the 48 hr withdrawal group. The changes of 5-HT level in the hypothalamus were similar to those in the striatum. These results suggest that the pharmacological actions of PCP and tolerance development to PCP may be related to the functional changes of serotonergic neuronal activity.
 ...
PMID:Effects of acute and chronic administrations of phencyclidine on the levels of serotonin and 5-hydroxyindoleacetic acid in discrete brain areas of mouse. 257 8

Electrophysiological studies were carried out to investigate the mechanism of action of phencyclidine [PCP; 1-(phenylcyclohexyl)piperidine] on a segmental monosynaptic reflex using isolated spinal cord preparations from neonatal rats. PCP and its related compounds produced a concentration-dependent depression of the monosynaptic reflex with a relative potency as follows: PCP = 1-[1-(2-thienyl)cyclohexyl]piperidine greater than 1-(1-m-aminophenylcyclohexyl)piperidine much greater than 1-(1-m-nitrophenylcyclo-hexyl)piperidine approximately MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate] much greater than (+)-N-allylnormetazocine. The N-methyl-D-aspartate receptor antagonists 2-amino-5-phosphonovalerate and 2-amino-7-phosphonoheptanoate had no effect on the monosynaptic reflex. The depression of the monosynaptic reflex by PCP was antagonized by serotonin (5-HT) receptor antagonists (methiothepin, spiperone and ketanserin) but unaffected by noradrenergic (phentolamine and timolol), dopaminergic (chlorpromazine and pimozide) and cholinergic antagonists (atropine and mecamylamine). Whereas 5-HT and a putative 5-HT releaser, p-chloroamphetamine, also depressed the monosynaptic reflex, the blockade of monoamine uptake by imipramine did not. Furthermore, pretreatment of rats with desipramine and 5,7-dihydroxytryptamine largely diminished the depression of the monosynaptic reflex by PCP and p-chloroamphetamine while enhancing the depressant action of 5-HT. These results suggest that PCP acts at sites located on presynaptic terminals of spinal serotonergic neurons, enhancing 5-HT release and thereby depressing the monosynaptic reflex.
 ...
PMID:Presynaptic activation of the spinal serotonergic system in the rat by phencyclidine in vitro. 274 96

Phencyclidine (PCP)-induced behaviors were compared with 5-methoxy-N,N-dimethyltryptamine (5-MeODMT)- and p-chloroamphetamine-induced behaviors in rats pretreated with ritanserin or 5,7-dihydroxytryptamine (5,7-DHT) in order to investigate whether PCP interacts with 5-hydroxytryptamine2 (5-HT2) receptors. Head-twitch and wet-dog shake induced by p-chloroamphetamine, a 5-HT releaser, and head-twitch induced by PCP were blocked completely by pretreatment with ritanserin, a specific 5-HT2 receptor blocker, but other behaviors induced by p-chloroamphetamine, PCP and 5-MeODMT, a 5-HT agonist, were not. The intensity of head-weaving, turning, backpedalling and hind-limb abduction induced by 5-MeODMT and the intensity of head-weaving, turning and head-twitch induced by PCP were markedly greater in the rats 2 weeks after the 5,7-DHT, a 5-HT neurotoxin-injection. Contrarily, 5-HT-mediated behaviors induced by p-chloroamphetamine were attenuated in the 5,7-DHT-treated rats. 5,7-DHT-treatment increased the number of 5-HT1 ([3H]-5-HT), 5-HT2 ([3H]ketanserin) and PCP ([3H]PCP) binding sites in the synaptic membrane of rat brain, but decreased the brain level of 5-HT (41% of control). These results may indicate that PCP as a 5-HT2 agonist induces head-twitch via 5-HT2 receptors, and that PCP induces head-weaving and turning via 5-HT1 receptors and/or some other mechanisms in rats.
 ...
PMID:Potentiation in phencyclidine-induced serotonin-mediated behaviors after intracerebroventricular administration of 5,7-dihydroxytryptamine in rats. 282 56

Ritanserin (0.125, 0.25, 0.5, 1.0 and 2.0 mg/kg s.c.), a selective serotonin (5-HT2) receptor antagonist, produced a dose-dependent inhibition of the head-twitch response induced in mice by phencyclidine (PCP) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). In contrast, ritanserin, dose dependently increased PCP- and 5-MeODMT-induced head-weaving. There was a significant inverse relationship between head-twitch and head-weaving responses. Pretreatment with p-chlorophenylalanine (PCPA, 300 mg/kg i.p.), a serotonin synthesis inhibitor, attenuated the head-weaving induced by the combination of PCP (12.5 mg/kg i.p.) and ritanserin but PCPA did not alter the 5-MeODMT-induced head-weaving. These results indicate that PCP induces head-weaving by interacting with a 5-HT receptor (possibly of the 5-HT1 subtype) indirectly after 5-HT release and induces head-twitch by interacting with 5-HT2 receptors directly.
 ...
PMID:Phencyclidine-induced head-weaving observed in mice after ritanserin treatment. 288 67

We investigated whether phencyclidine (PCP)-induced head-twitch was antagonized in rats by ritanserin, a selective serotonin2 (5-HT2) receptor antagonist, to confirm the involvement of 5-HT neurons in PCP action and to discover whether PCP could protect the binding sites of [3H]PCP and [3H]ketanserin from the inhibitory effect of protein-modifying reagents which affect sulfhydryl groups. PCP (7.5, 10 and 12.5 mg/kg, i.p.)-induced head-twitch was completely antagonized by ritanserin (1 mg/kg, s.c.). Scatchard plots of specific [3H]PCP and [3H]ketanserin binding showed that sulfhydryl-modifying reagent, N-ethylmaleimide (NEM, 100 microM) caused a significant decrease in Bmax without changing Kd. PCP (10 microM) and ritanserin (1 microM) protected [3H]PCP and [3H]ketanserin binding sites from the decrease in the number induced by NEM (100 microM). 5-HT protected [3H]5-HT binding sites from inactivation by NEM, but PCP and ritanserin did not show any effect. On the basis of the present findings, it is concluded that PCP can interact with 5-HT2 receptors directly or allosterically, and 5-HT2 receptors may locate at PCP binding sites in membranes.
 ...
PMID:Protection with phencyclidine against inactivation of 5-HT2 receptors by sulfhydryl-modifying reagents. 313 11

In rats treated with phencyclidine (PCP) repeatedly (PCP 10 mg/kg per day for 14 days), the back-pedalling, head-weaving and turning induced by PCP were attenuated (tolerance), while PCP-induced sniffing, rearing and ambulation were potentiated (supersensitivity). The behavior induced by the direct and indirect serotonin (5-HT) agonists, 5-methoxy-N,N-dimethyltryptamine and p-chloroamphetamine, was attenuated, while the sniffing, rearing or licking induced by the direct and indirect dopamine (DA) agonists, apomorphine and methamphetamine, were potentiated in the chronic PCP-treated rats. The DA and 5-HT contents in the nucleus accumbens and the ratio of HVA to DA in the striatum increased following the repeated PCP administration. Pentobarbital-induced sleep time did not change in the chronic PCP-treated rats as compared with the control rats. In addition, there was no significant difference between the disappearance rate of PCP in the brain of the rats treated with PCP repeatedly and the rate in the control rats. These results suggest that functional changes in the dopaminergic and serotonergic neuronal systems develop on repeated administration of PCP but that such changes do not develop in the hepatic drug-metabolizing system. In addition, tolerance develops in the serotonergic neuronal system while supersensitivity develops in the dopaminergic neuronal system. Biochemical findings suggest that increased mesolimbic dopaminergic neuronal function plays an important role in the development of the supersensitivity.
 ...
PMID:Development of tolerance and supersensitivity to phencyclidine in rats after repeated administration of phencyclidine. 356 23

This study was designed to determine the action sites of phencyclidine (PCP) involved in the development of behaviors such as head-weaving, immobility, turning and backpedalling in relation to dopaminergic and serotonergic neuronal functions. Injection of PCP into the caudate nucleus or prefrontal cortex dose-dependently produced head-weaving, although the injection of PCP into the nucleus accumbens failed to produce head-weaving. The intensity of head-weaving induced by injection of PCP into the prefrontal cortex was relatively high when compared to that induced by injection of PCP into the caudate nucleus or lateral ventricle. Pretreatment with p-chlorophenylalanine (300 mg/kg), a serotonin (5-HT) synthesis inhibitor, attenuated head-weaving induced by injection of PCP into the prefrontal cortex. Injection of PCP (50-100 micrograms) into the prefrontal cortex also produced immobility for 5 min post-injection. Rats pretreated with pimozide (1 mg/kg), a dopamine (DA) antagonist, also produced immobility after the injection of PCP into the prefrontal cortex and this effect was attenuated by pretreatment with ritanserin, a 5-HT2 receptor antagonist. On the other hand, pretreatment with methamphetamine attenuated PCP (5 and 7.5 mg/kg)-induced turning and backpedalling but not head-weaving. Pretreatment with large doses of apomorphine, a DA agonist, also greatly attenuated PCP (7.5 mg/kg)-induced behaviors, i.e. head-weaving, turning and backpedalling. These effects of DA agonists were prevented by haloperidol (0.25 mg/kg), a DA antagonist. These results suggest that PCP-induced turning and backpedalling may be mediated by reducing dopaminergic transmission, although PCP-induced head-weaving and immobility may be produced by increasing serotonergic transmission in the prefrontal cortex.
 ...
PMID:Role of dopaminergic and serotonergic neuronal systems in the prefrontal cortex of rats in phencyclidine-induced behaviors. 357 18

This study was designed to assess whether phencyclidine (PCP) produces dopamine (DA)-dependent behaviors such as licking, biting and gnawing at low doses after withdrawal from chronic haloperidol (HAL) treatment in rats. Low doses of PCP (2.5 and 5 mg/kg) produced licking, gnawing, biting and self-biting in rats after withdrawal from chronic HAL treatment, which were not observed in the vehicle-pretreated rats given PCP at the same dose range. These behaviors were similar to DA-dependent behaviors produced by methamphetamine and apomorphine in rats after withdrawal from chronic HAL treatment. The PCP-induced behaviors were attenuated by acute pretreatment of DA antagonist, HAL (0.25 mg/kg, IP). Furthermore, at doses of 5 or 7.5 mg/kg, PCP-induced head weaving and backpedalling, which were mediated by both DA and serotonin (5-HT) neurons, significantly increased in rats after withdrawal from chronic HAL-treatment. These results suggest that dopaminergic systems play an important role for PCP-induced behavioral responses.
 ...
PMID:Phencyclidine-induced dopamine-dependent behaviors in chronic haloperidol-treated rats. 408 Jul 67


1 2 3 4 5 6 7 8 9 10 Next >>