Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

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.
...
PMID:The involvement of sigma and phencyclidine receptors in the action of antipsychotic drugs. 133 17

Prepulse inhibition of acoustic or tactile startle (PPI), a form of sensorimotor gating, occurs when a weak prestimulus precedes a startling stimulus and inhibits the startle response. Studies of PPI have revealed that schizophrenic patients exhibit a deficit in this form of sensorimotor gating. In rats, PPI is blocked by dopamine agonists such as apomorphine or quinpirole, effects that are antagonized by haloperidol. Phencyclidine (PCP) has been suggested as a possible model psychotogen and produces a deficit in PPI that is similar to what is observed in schizophrenic patients. Dizocilpine is an anticonvulsant drug that, like PCP, is a noncompetitive antagonist of N-methyl-D-aspartate (NMDA)-induced excitations in brain and also disrupts PPI. In the present study, PPI of acoustic and tactile startle was measured in male Sprague-Dawley rats after injections of 5.0 mg/kg PCP with or without pretreatment with 0.02 or 0.1 mg/kg haloperidol, or with 0.5 mg/kg dizocilpine with or without pretreatment with 0.1 mg/kg haloperidol. The 0.1 mg/kg dose of haloperidol blocks the effects of apomorphine or quinpirole on PPI in rats. Startle was elicited by noise bursts at 105 or 120 dB or by air-puffs (tactile) and was inhibited by 75 or 85 dB prepulse stimuli presented 100 msec before the startle stimuli. The different eliciting stimuli produced different levels of startle in both control and drug-treated animals. Both NMDA antagonists significantly reduced the amount of PPI induced by the 75 dB prestimulus, independently of the level of startle responses elicited by the startle stimuli. Haloperidol did not block the disruption of PPI induced by either PCP or dizocilpine. In addition, PCP was unable to block PPI when the 85 rather than the 75 dB prepulse was used to inhibit either acoustic or tactile startle. These results confirm that putative NMDA antagonists inhibit sensorimotor gating in rats and suggest that these effects are not mediated by the activation of central dopamine systems.
...
PMID:Failure of haloperidol to block the effects of phencyclidine and dizocilpine on prepulse inhibition of startle. 183 31

Haloperidol and (+)-3-PPP, compounds with known affinity for the sigma-receptor, have been examined for their ability to reduce the excitatory actions of N-methyl-DL-aspartate (NMDLA), quisqualate and kainate on rat spinal neurons in-vivo. The actions of (-)-3-PPP were also tested. Haloperidol was injected intravenously whereas the 3-PPP enantiomers were administered by microelectrophoresis. Haloperidol had little effect on excitations evoked by NMDLA, quisqualate or kainate whereas both (+)- and (-)-3-PPP usually enhanced, non-selectively, responses to all three excitatory amino acid analogues. The results support suggestions that phencyclidine (PCP)-like compounds with affinity for both PCP and sigma-receptors reduce neuronal excitations mediated by the N-methyl-D-aspartate (NMDA) receptor via a selective effect at the PCP site.
...
PMID:Failure of sigma-receptor ligands to reduce the excitatory actions of N-methyl-DL-aspartate on rat spinal neurons in-vivo. 196 52

The functional effects of sigma and PCP receptor ligands were examined in the perfused rat tail artery. The following ligands were studied: haloperidol; (+)-3-PPP [(+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine]; (+-)-BMY 14802 [(+-)-alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol]; DTG [1,3-di-orthotolyl-guanidine]; rimcazole (BW 234U) [cis-9-[3-(3,5-dimethyl-1-piperazinyl)propyl]carbazole dihydrochloride]; (+)-SKF 10047 [(+)-N-allyl-N-normetazocine]; TCP, [1-[1-(2-thienyl)cyclohexyl] piperidine]; and MK 801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate]. (+)-3-PPP, (+)-SKF 10047, MK 801 and TCP potentiated contractile responses to norepinephrine, an effect which was blocked by cocaine implying an action of these agents on monoamine uptake. In the presence of cocaine an additional postjunctional inhibitory action of (+)-3-PPP and (+)SKF 10047 on norepinephrine-induced contractile responses was unveiled. In contrast, haloperidol, (+/-)-BMY 14802, rimcazole and DTG inhibited contractile responses to norepinephrine. Haloperidol, (+/-)-BMY 14802 and (+)-SKF 10047 (+ uptake blockade) also inhibited contractile responses to serotonin. The order of potency for inhibition of norepinephrine-induced contractions was haloperidol greater than (+/-)-BMY 14802 greater than (+)-3-PPP greater than rimcazole greater than (+)-SKF 10047 (+ uptake blockade) greater than DTG. These studies demonstrate the lack of selectivity of many sigma and PCP ligands, significant effects on norepinephrine uptake, as well as the potential utility of the rat tail artery to explore the functional properties of these ligands.
...
PMID:Multiple vascular effects of sigma and PCP ligands: inhibition of amine uptake and contractile responses. 215 42

Phencyclidine (PCP, 10 mg/kg s.c.) produced a marked reduction in the extracellular concentrations of DOPAC and HVA in the rat striatum in vivo, as measured by differential pulse voltammetry. In contrast, extracellular 5-HIAA levels were significantly elevated. Haloperidol (1 mg/kg i.p.) increased DOPAC and HVA, and reduced 5-HIAA, in agreement with previous studies. When PCP and haloperidol were injected together, the effects of PCP were abolished. These results suggest that PCP administration leads to increased activation of dopamine receptors, which results in a decrease in striatal dopamine turnover and an increase in striatal serotonin turnover.
...
PMID:Analysis of extracellular DOPAC, HVA and 5-HIAA in rat striatum in vivo by differential pulse voltammetry: effect of phencyclidine, haloperidol and their coadministration. 244 34

We have used a variety of selective radioligands to identify and localize sigma- and phencyclidine (PCP)-binding sites in rat endocrine organs. [3H]Haloperidol-labeled sigma-receptors were identified in membrane homogenates of rat pituitary, adrenal, testis, and ovary which had kinetic and pharmacological characteristics similar to those of the well characterized sigma-receptors in rat cerebellum. The highest density of sigma-receptors was present in the ovary, with progressively lower densities present in the testis, pituitary, adrenal, and cerebellum, respectively. In autoradiographic studies, sigma-receptors [labeled with d-3-(3-hydroxyphenyl)N-(1-propyl-2,3-[3H]piperidine or [3H]1,3-di-(2-tolyl)guanidine] were discretely localized within the endocrine tissues. In the pituitary, the highest density of sigma-receptors was found in the anterior lobe. In the adrenal, sigma-receptors were localized primarily in the cortex. In the testis, sigma-receptors were present in highest concentrations in the ductuli efferentes and ductus epididymis; lower densities of binding sites were present in the seminiferous tubules, and no binding was seen in the interstitial tissue. In the ovary, sigma-receptors were localized in high density in the maturing follicles, and lower densities were present in resting follicles. After hypophysectomy, there were relative increases in the densities of sigma receptors in the remaining tissue in the adrenal gland and testis. In contrast, hypophysectomy resulted in a marked depletion of sigma-binding sites in the ovary. The data from hypophysectomized rats indicate that the highest densities of sigma-receptors in the ovary are localized to (LH-dependent) maturing follicles, while sigma-binding sites in adrenal and testis are localized to cells that are not dependent on trophic maintenance by the pituitary. In contrast, high affinity PCP receptors were not detected in pituitary, adrenal, testis, or ovary either by homogenate binding studies with 3,4-[3H]N-[1-(2-thienyl)cyclohexyl]piperidine or in vitro autoradiography using 3,4-[3H]N-[1-(2-thienyl)cyclohexyl]piperidine and d-[3H]5-methyl-10,11-dihydro-5H-dibenzo-[a,d] + cyclohepten-5,10-imine. In summary, the data suggest that the reported endocrine effects of PCP and the prototypic sigma-receptor agonist N-allylnormetazocine are probably mediated either through direct action on sigma-receptors in the pituitary and/or target endocrine organs or by actions on sigma- and/or PCP receptors in brain.
...
PMID:Sigma-receptors in endocrine organs: identification, characterization, and autoradiographic localization in rat pituitary, adrenal, testis, and ovary. 253 73

We studied the effects of several prototypic sigma site ligands on the binding of [3H]dextromethorphan ([3H]DM) to guinea pig brain. Haloperidol, 3-(-3-Hydroxyphenyl)-N-(1-propyl)piperidine [+)-3-PPP) and (+)-N-allyl-N-normetazocine [+)-NANM or (+)-SKF10,047), which are potent sigma site ligands, showed high affinity for [3H]DM binding sites. The rank order of potency of sigma ligands, as indicated by the Ki values for the high-affinity sites is: haloperidol greater than (+)-pentazocine greater than (+)-cyclazocine greater than (+)-SKF10,047 greater than (-)-butaclamol much greater than (+)-butaclamol greater than (-)-SKF10,047. This rank order of potency is similar to that for the sites labeled with [3H](+)-3-PPP and [3H](+)-SKF10,047. The (+)-isomers of several benzomorphans displayed higher affinity than the (-)-isomers. (-)-Butaclamol competed against [3H]DM binding more effectively than the (+)-isomer, displaying the same stereospecificity shown for sigma sites. The findings reported here demonstrate that there are previously unrecognized similarities between DM and sigma sites. It is evident that further exploration of the DM, sigma and phencyclidine (PCP) sites will be necessary to establish the physiological role and therapeutic potential of these sites.
...
PMID:The effect of prototypic sigma ligands on the binding of [3H]dextromethorphan to guinea pig brain. 253 77

Phencyclidine (PCP) has been reported to suppress a variety of immune functions in vitro. Because PCP binds with high affinity to both PCP and sigma receptors, the identity of the receptor(s) mediating the immunological effects of PCP is unknown. The aim of the present study was to identify and characterize the sites of PCP action (sigma and/or PCP receptors) in human peripheral blood leukocytes (PBL) using [3H]haloperidol or 1,3 di(2-([5-3H]tolyl)guanidine ([3H]DTG) to specifically label sigma receptors and 3,4-[3H]-(N)-[1-(2-thienyl)-cyclohexyl]-piperidine ([3H]TCP) to specifically label PCP receptors. [3H]Haloperidol binding was saturable and of high affinity with comparable KD values in human PBL (0.44 +/- 0.10 nM) and rat cerebellum (0.51 +/- 0.09 nM). Similarly, [3H]DTG binding was saturable with comparable KD values of 29.5 +/- 3.5 and 26.4 +/- 3.6 nM in rat cerebellum and human PBL, respectively. In contrast, there was a notable absence of [3H]TCP-labeled PCP receptors in human PBL and rat cerebellum. In competition studies, the pharmacologic profile of [3H]haloperidol-labeled sigma receptors in human PBL was virtually identical with that in rat cerebellum (slope, 0.87; correlation coefficient, 0.96); the rank order of potency of competing drugs was haloperidol greater than l-butaclamol = pentazocine greater than d-3-(hydroxyphenyl)-N-(1-propyl)-piperidine greater than DTG = d-butaclamol = d-SKF 10,047 greater than levallorphan greater than or equal to PCP greater than or equal to l-SKF 10,047 greater than TCP greater than MK-801.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Initial identification and characterization of sigma receptors on human peripheral blood leukocytes. 284 60

Binding of the opiates (+)-[3H]SKF 10,047 [N-allylnormetazocine; (+)-[3H]SKF] and (+)-[3H]ethylketocyclazocine [(+)-[3H]EKC] were compared to mu, kappa and delta and phencyclidine (PCP) receptor binding in guinea pig brain membranes. (+)-[3H]SKF and (+)-[3H]EKC binding were not blocked by naloxone, and had different drug selectivity compared to mu, kappa and delta binding sites. The number of binding sites, drug selectivity and region distribution in brain were similar for (+)-[3H]SKF and (+)-[3H]EKC. Sigma opiates that are associated with psychotomimetic activities, such as pentazocine, cyclazocine, SKF 10,047 and bremazocine, were potent inhibitors of (+)-[3H]SKF and (+)-[3H]EKC binding. Haloperidol was the most potent inhibitor of (+)-[3H]SKF binding. Haloperidol and sigma opiates demonstrated biphasic displacement of [3H]PCP binding, suggesting that [3H]PCP labelled two sites. PCP had a similar affinity for both (+)-[3H]SKF and [3H]PCP binding sites in the presence of 100 mM NaCl. The highest concentrations of (+)-[3H]SKF and (+)-[3H]EKC bindings sites were in the hypothalamus, anterior pituitary, midbrain, pons and medulla.
...
PMID:(+)-[3H]SKF 10,047, (+)-[3H]ethylketocyclazocine, mu, kappa, delta and phencyclidine binding sites in guinea pig brain membranes. 298 89

Amphetamine (1.0-7.0 mg/kg), cocaine (5.0-40.0 mg/kg) and phencyclidine (1.0-7.0 mg/kg) increased acoustic startle responding in mice. These drugs, however, had varying effects on habituation of the startle response after repeated exposure to the auditory stimulus. The primary effect of phencyclidine was to disrupt the habituation process, whereas increased startle responding after cocaine developed without modification of the habituation curve. Amphetamine facilitated acoustic startle at all doses, and after administration of 3.0 mg/kg a significant response sensitization as a function of repeated stimulus presentation was evident. Consistent with previous reports the excitatory effects of cocaine and amphetamine on acoustic startle were blocked by pretreatment with haloperidol. Haloperidol, which decreased startle responding, attenuated the facilitating effects of PCP on acoustic startle as well. Chronic exposure to amphetamine, cocaine and phencyclidine had differential effects on startle responding. The facilitating effects of amphetamine on startle were further enhanced after long-term exposure to the drug and the sensitizing effect of repeated amphetamine exposure was observed only when animals were tested with amphetamine. In contrast, tolerance developed after chronic exposure to both cocaine and phencyclidine, and the response attenuation was evident when animals were tested for acoustic startle after cocaine, amphetamine and phencyclidine.
...
PMID:Sensitization to amphetamine and tolerance to cocaine and phencyclidine stimulation in mice. 380 18


1 2 3 4 Next >>

---