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)

An atypical antipsychotic drug clozapine and a selective sigma antagonist BMY 14802 were significantly less effective in the behavioural experiments (against apomorphine, d-amphetamine and MK-801), as well in the radioligand binding studies against 3H-spiperone (dopamine2-receptors) and 3H-haloperidol (sigma receptors) in the rat brain, as compared to a typical antipsychotic compound haloperidol. Contrary to haloperidol and BMY 14802, clozapine was a relatively selective antagonist of MK-801-induced motor excitation in the mouse. A nearly 3-fold lower dose of clozapine was needed to block the effect of MK-801 (6.4 mumol/kg) as compared to the action of amphetamine (17 mumol/kg). Haloperidol and clozapine, but not BMY 14802, antagonized apomorphine-induced aggressiveness in the rat. After long-term treatment (for 15 days) with BMY 14802 (10 mg/kg daily), haloperidol (0.5 mg/kg daily) and clozapine (10 mg/kg daily) the motor depressant effect of apomorphine (0.15 mg/kg) was reversed. Chronic haloperidol treatment, but not administration of BMY 14802 and clozapine, increased the number of dopamine2-receptors in the rat brain. BMY 14802 caused upregulation of sigma receptors in frontal cortex, whereas haloperidol induced the opposite change in cerebellum. Repeated treatment with clozapine significantly augmented the motor stimulating effect of MK-801 in rats. Simultaneously with a behavioural change the density of 3H-TCP binding sites in the rat forebrain was elevated after long-term treatment with clozapine, probably indicating the involvement of PCP binding sites at NMDA channel in the action of clozapine.
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PMID:The involvement of sigma and phencyclidine receptors in the action of antipsychotic drugs. 133 17

The effects of continuous i.v. phencyclidine (PCP) infusion and withdrawal on operant behavior were studied in rhesus monkeys. The monkeys were trained to lever press under a fixed-ratio 100 schedule of food presentation. They responded under this schedule during four daily 30-min periods conducted every 6 hr. After at least 5 days of continuous saline infusion through indwelling i.v. catheters, the subjects received 10 days of continuous infusion of 0.05 mg/kg/hr of PCP. During chronic PCP, rates of responding increased above saline control values. When saline was substituted for PCP, responding was suppressed markedly. This suppression of responding occurred within 8 hr of saline substitution and lasted several days. Mild signs of withdrawal were seen within 3 hr after saline substitution and dissipated by 48 hr. These signs included muscle tremors, oculomotor hyperactivity and increased aggressiveness. After responding during saline infusion had returned to control levels, continuous PCP infusion was resumed. Withdrawal effects on behavior decreased in intensity after repeated withdrawals and it was necessary to raise the infusion dose to produce consistent withdrawal disruption of behavior. Withdrawal-induced disruption in responding was reversed by acute pretreatment with PCP (0.01-0.3 mg/kg i.m.) in a dose-related fashion. Presession administration of naloxone (0.1-1.0 mg/kg i.m.) during chronic PCP infusion failed to precipitate withdrawal signs or disrupt operant responding, suggesting that PCP dependence is not of the opioid type. The results of this study indicate that operant behavior is disrupted during withdrawal from chronic PCP and can be used as evidence of behavioral dependence.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Behavioral dependence produced by continuous phencyclidine infusion in rhesus monkeys. 654 Mar 4

Previous studies indicate that PCP users have different characteristics from other drug users and that female PCP use is more common than use among males. Furthermore, there is evidence that those who respond to PCP with violence may differ from those who do not. This study attempted to examine comprehensively the psychological, behavioral, and background factors among female jail inmates that may contribute to a PCP preference and subjects' perception of various behavioral states while using PCP. Female PCP users were further examined relative to male PCP users to differentiate them on the basis of these perceptual factors. A distinction was further made between females and males prone to PCP-induced violence and those who do not become violent with respect to the above psychological and behavioral measures. Our results showed differences between male and female PCP users that are discrepant with the assumption that men and women perceive similar drug-related experiences. In particular, female PCP using subjects reported more dysphoria and aggressiveness when not using PCP, while male subjects were more likely to report aggressive behavior and dysphoria under the influence. Overall, these results suggest that males who prefer PCP may be self-stimulating and females who prefer PCP may be attempting to self-medicate.
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PMID:Female PCP-using jail detainees: proneness to violence and gender differences. 873 May 18

The non-canonical Wnt/planar cell polarity (Wnt/PCP) pathway plays a crucial role in embryonic development. Recent work has linked defects of this pathway to breast cancer aggressiveness and proposed Wnt/PCP signalling as a therapeutic target. Here we show that the archetypal Wnt/PCP protein VANGL2 is overexpressed in basal breast cancers, associated with poor prognosis and implicated in tumour growth. We identify the scaffold p62/SQSTM1 protein as a novel VANGL2-binding partner and show its key role in an evolutionarily conserved VANGL2-p62/SQSTM1-JNK pathway. This proliferative signalling cascade is upregulated in breast cancer patients with shorter survival and can be inactivated in patient-derived xenograft cells by inhibition of the JNK pathway or by disruption of the VANGL2-p62/SQSTM1 interaction. VANGL2-JNK signalling is thus a potential target for breast cancer therapy.
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PMID:Identification of p62/SQSTM1 as a component of non-canonical Wnt VANGL2-JNK signalling in breast cancer. 2675 71