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)

A variety of drugs were screened to determine which were capable of blocking the behavioral stimulation produced in mice by acute administration of phencyclidine (PCP). Chlorpromazine and clozapine blocked PCP-induced stimulation, while haloperidol, reserpine, and alpha-methyl-p-tyrosine did not. The GABA receptor agonists imidazole acetic acid and muscimol blocked PCP, but other drugs that influence GABA, such as dipropylacetic acid, baclofen, and diazepam, were ineffective. Yohimbine and methysergide also blocked PCP in high dosages, but other drugs with comparable alpha-noradrenergic and serotonergic blocking properties (phentolamine, cyproheptadine, and cinnanserin) were ineffective. Cholinergic and anticholinergic drugs, beta-noradrenergic and opiate antagonists and nonspecific sedatives and convulsants were also ineffective. These findings suggest that chlorpromazine, clozapine, yohimbine, and methysergide may share a property that is unlike their primary known modes of action on dopaminergic, alpha-noradrenergic, and serotonergic neurotransmitter systems, and that this property accounts for their ability to block PCP. However, the effectiveness of GABA agonists appears to be mediated through direct activation of GABA receptors. It is suggested that chlorpromazine and imidazole acetic acid should be considered as possible drug treatments for PCP toxicity.
...
PMID:Neuropharmacological studies of phencyclidine (PCP)-induced behavioral stimulation in mice. 610 51

PCP-GABA, an analogue of the neurotransmitter amino acid, GABA, is as effective a stimulant of vagal centers and acid secretion as sham feeding. Insulin hypoglycemia, a test hitherto widely used for the cephalic phase, is unsafe and nonspecific because it also stimulates catecholamine release which affects gastrin secretion. PCP-GABA, unlike insulin, causes no tachycardia or hypoglycemia; however, the major advantage of PCP-GABA is that it can be used safely intraoperatively to assess completeness of vagotomy. Its muscle relaxant action is an additional advantage in this regard. As an intraoperative test, PCP-GABA is given intravenously shortly after induction of anesthesia to stimulate acid secretion and to reduce gastric mucosal pH, which is measured by an intraluminal combination electrode. The electrode can be moved around through the intact gastric wall to take measurements from multiple sites. When vagotomy is complete, gastric mucosal pH increases to over 6. This test works well in the dog. We hope to assess its clinical use in the near future.
...
PMID:A new intraoperative test for completeness of vagotomy: the PCP-GABA (beta-parachlorophenol-gamma-aminobutyric acid) test. 636 46

Parenteral administration of beta-(p-chlorophenyl)-gamma-aminobutyric acid (PCP-GABA), a lipophilic GABA mimetic, has been shown to aggravate stress-induced ulcerations in the rat. Since acid hypersecretion may be a possible mechanism for this, we studied the effect of graded doses of PCP-GABA on rat gastric acid secretion. The stimulatory effect of PCP-GABA was found to be dose-dependent, long-acting, and massive, exceeding the maximal effects of histamine and bethanechol. The acid stimulant effect of PCP-GABA was completely abolished not only by atropine but also by truncal vagotomy. Vagotomized, PCP-GABA-treated animals responded to bethanechol, suggesting that a peripheral (cellular) mechanism is not involved. We conclude that PCP-GABA acts centrally to activate vagal centers and to cause acid hypersecretion. Although hypersecretion of acid caused by PCP-GABA may be involved in the observed aggravation of stress-induced ulceration in the rat stomach, evidence for this has yet to be provided.
...
PMID:GABA-mimetic effect on gastric acid secretion. Possible significance in central mechanisms. 682 81

Pretreatment (IP) of mice with (-) baclofen, muscimol, 4,5,6,7-tetrahydroisoxazolo (S,4-c) pyridin-3-ol hydrate (THIP), aminooxyacetic acid (AOAA) or gamma-acetylenic GABA caused a dose-dependent inhibition of thelocomotor stimulant effect of phencyclidine (PCP, 8 mg/kg). Although (-) baclofen was found to be the most effective PCP antagonist, its (+) isomer was inactive. The maximum blocking effect of AOAA was seen in animals treated 3 and 6 hr earlier. Except for gamma-acetylenic GABA, none of these drugs significantly blocked the locomotor stimulant effect of d-amphetamine (3 mg/kg, IP). Diazepam reduced d-amphetamine response, but failed to influence PCP-induced stimulation. The locomotor stimulant effect of PCP, unlike that of d-amphetamine, may be the result of a specific GABA antagonistic effect at certain dopamine-rich areas of the brain. It seems that (-) baclofen may prove to be useful in the management of PCP intoxication. Administration of higher doses of PCP (20 and 50 mg/kg) in mice pretreated with (-) baclofen resulted in the development of surgical anesthesia manifested as the loss of a) righting reflex, b) pain sensation and c) corneal reflex. The duration of the general anesthetic response was found to be a function of the doses of both (-) baclofen and PCP. The possible use of (-) baclofen as an adjuvant to general anesthetic is discussed.
...
PMID:Interaction between phencyclidine (PCP) and GABA-ergic drugs: clinical implications. 736 54

The effects of handling and handling combined with phencyclidine (PCP) treatment on GABAergic neurotransmission were studied in Sprague-Dawley rats. The animal material consisted of handling-habituated (HH, for 11 d), acutely handled (naive, N), handling-habituated and PCP-treated (10 mg kg-1 i.p., HH + PCP) and acutely handled (naive) PCP-treated (N + PCP) and unhandled 'control' rats. The binding of [3H]GABA and [3H]flunitrazepam (FLU) was studied with membranes and the release of [3H]GABA with slices prepared from the striatum and frontal cortex. In the striatum the maximal binding capacity (Bmax) and the binding constant (KD) of [3H]GABA were the same in N and HH rats, but in the frontal cortex KD was lower in N rats. KD constants of [3H]FLU were significantly lower in both brain areas in N rats than in HH rats. After PCP treatment both Bmax and KD for [3H]FLU increased in these two brain areas in handling-habituated rats, whereas Bmax of [3H]GABA diminished. Neither handling nor PCP had any effect on [3H]GABA release from striatal and frontal cortical slices. Handling prior to killing thus affects differently the GABAergic parameters studied and modulates the PCP-induced effects.
...
PMID:The effect of phencyclidine on [3H]GABA and [3H]flunitrazepam binding in the brain of naive and handling-habituated rats. 762 66

The effect of phencyclidine (PCP) on the gamma-aminobutyric acid-ergic (GABAergic) transmission in the striatum of freely-moving rats was investigated using an in vivo microdialysis. The high potassium (100 mM) increased the extracellular GABA level to 4000% of the basal level. Although the basal GABA level in the striatal dialysate did not show either calcium dependency or tetrodotoxin (TTX) sensitivity, the high potassium evoked GABA level was reduced by 82% under calcium-free conditions (with 12.5 mM magnesium) and by 54% in the presence of 10 microM TTX. The systemic administration of PCP (7.5 mg/kg) or the local perfusion of PCP (100 microM and 1 mM) significantly inhibited the high potassium evoked GABA release in the rat striatum. The local perfusion of MK-801 (10 microM and 100 microM), a more potent and selective N-methyl-D-aspartate (NMDA) receptor antagonist, also inhibited the high potassium evoked striatal GABA release. These drugs did not show any significant effect on the basal extracellular GABA level. NMDA (1 mM) either partly or completely blocked the effect of PCP (1 mM) or MK-801 (100 microM) on the high potassium evoked striatal GABA release. On the other hand, nomifensine (100 microM), a dopamine uptake blocker, did not show any effect on the high potassium evoked GABA release. These results suggest that PCP inhibited the striatal GABAergic neuronal transmission through its antagonism of the NMDA receptor.
...
PMID:The effect of phencyclidine on the basal and high potassium evoked extracellular GABA levels in the striatum of freely-moving rats: an in vivo microdialysis study. 772 33

Neuropeptide Y-like immunoreactivity (NPYLI) in the frontal cortex and nucleus accumbens was significantly decreased after acute and multiple administrations of phencyclidine-HCl (PCP). The role of dopamine, serotonin and sigma receptors in these PCP-induced effects was evaluated. Neither the dopamine D1 antagonist SCH 23390 nor the D2 antagonist sulpiride by itself altered cortical neuropeptide systems, but in combination they totally blocked the PCP-induced changes. In contrast, sulpiride alone significantly decreased accumbens NPYLI content and enhanced the PCP-induced decreases, whereas SCH 23390 alone had no effect on accumbens NPYLI levels but did attenuate PCP-induced effects. Neither depletion of serotonin nor blockage of the sigma "receptor" had any effect on PCP-induced changes in either structure. The effects of the selective, noncompetitive N-methyl-D-aspartate receptor antagonist MK-801 on cortical and accumbens NPYLI content were similar to those of PCP, suggesting an N-methyl-D-aspartate receptor mechanism in these effects. Administration of gamma-aminobutyric acid-transaminase (GABA-T) inhibitors, gamma-vinyl-GABA (GVG, vigabatrin, MDL 71,754) or aminooxyacetic acid alone had no effect on cortical NPYLI content; however, administration of aminooxyacetic acid alone decreased accumbens NPYLI levels. Co-administration of these GABA-T inhibitors with PCP completely blocked PCP-induced cortical NPYLI decreases and attenuated NPYLI changes in the accumbens. These data suggest that limbic neuropeptide systems are differentially modulated by N-methyl-D-aspartate and dopaminergic activity and that glutamatergic influences on cortical and accumbens NPY systems are mediated, at least in part, by GABAergic mechanisms.
...
PMID:Differential regulation of neuropeptide Y systems in limbic structures of the rat. 824 45

We measured [125I] iomazenil binding, labeling the central-type benzodiazepine receptor in 37 discrete rat brain areas following single (7.5 mg/kg, i.p.) and repeated (7.5 mg/kg/day x 14 days, i.p.) treatment with phencyclidine (PCP), a non-competitive antagonist of the N-methyl-D-aspartate(NMDA)-type glutamate receptor, using in vitro quantitative autoradiographic receptor binding assay. Both single and repeated PCP treatment produced heterogeneous changes in the rat brain in a similar manner, the magnitude of change in [125I] iomazenil binding being generally greater in the repeated treatment group than in the single treatment group. A significant increase in [125I] iomazenil binding was observed in the superficial layer (layer I-IV) of the parietal cortex in both of the PCP treatment groups and the CA1 of the hippocampus of the repeated PCP-treated group. There was a significant decrease in [125I] iomazenil binding in the piriform cortex of the repeated PCP-treated group. These results suggest that the blockade of NMDA receptor-mediated glutamatergic neurotransmission by PCP produces the compensational alterations in the central-type benzodiazepine receptor antagonist binding, and that the observed diversity may be due to dissimilar modes of organizations between glutamatergic and the GABA(gamma-aminobutyric acid)-benzodiazepine receptor complex.
...
PMID:The effects of single and repeated phencyclidine administration on [125I] iomazenil binding in the rat brain. 888 87

Beta-phenyl-ethylamine (PEA) at dose of 50 mg/kg inhibits spontaneous, motor activity in mice. CPP- (+/-)-3-(2-Carboxypiperazin-4-yl)-propyl-1-phosphonic acid, a selective and competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, in doses of 0.2-10 mg/kg dose-dependently antagonizes this inhibitory effect of PEA. This effect of CPP appeared to be selective because the inhibitory action of PEA was not altered by pretreament with noncompetitive antagonists of NMDA receptors, such as dizocilpine (MK-801), phencyclidine (PCP), 1-phenylcyclohexylamine (PCA) or by antagonists of other behavioral effects of PEA such as haloperidol, baclofen and phenibut (beta-phenyl-GABA). CPP failed to antagonize the inhibitory effect of other tested drugs such as diazepam, haloperidol, baclofen and phenibut. Intracerebroventricularly administered NMDA (0.2 microM), an agonist of NMDA receptors, suppressed the antagonistic effects of CPP against PEA. This suggests that anti-PEA effect of CPP is related to NMDA receptors. Anti-PEA effect of CPP is not due to accelerated deamination of PEA in CPP-treated mice. When small doses of PEA (5 and 10 mg/kg) and CPP (0.2 and 1 mg/kg) were used, the synergism of two drugs was observed. CPP (1 mg/kg) and deprenyl (0.5 mg/kg) an inhibitor monoamine oxidase of B type (MAO-B), had additive effects on PEA-induced inhibition of locomotion. This effect was not associated with any further inhibition of activity of brain MAO-B (over the inhibition induced by deprenyl alone-by 65%) under high (80 microM) or low (4.3 microM) concentration of PEA as a substrate in the medium. Mechanism of the interaction of CPP and PEA, two drugs belonging to different groups of biologically active compounds, deserves further studies.
...
PMID:Modulation of the inhibitory effect of phenylethylamine on spontaneous motor activity in mice by CPP-(+/-)-3-(2-carboxypiperazin-4-YL)-propyl-1-phosphonic acid. 905 75

To evaluate the discriminative stimulus effects of a direct-acting GABAA agonist, seven rats were trained to discriminate 1 mg/kg IP muscimol from saline under a two-lever fixed ratio (FR) 20 schedule of food reinforcement. The direct GABAA agonist THIP (4,5,6,7-tetrahydro-isoxazolo [5, 4,c]-pyridin-3-ol) produced increases in muscimol lever responding and substituted for muscimol in all subjects. Unlike results with muscimol, the highest levels of muscimol lever responding following THIP administration were often produced at doses which also decreased rates of responding. The GABAB agonist baclofen and the indirect-acting GABAA agonists pentobarbital and midazolam produced substitution for muscimol in some subjects, but not in others. The non-competitive NMDA antagonist phencyclidine (PCP) produced mixed results in these rats, from partial to full substitution (both dose-dependently and exhibiting in lack of dose-dependence) in some animals and a complete failure to substitute in another. The selective GABAA antagonist bicuculline dose-dependently blocked the muscimol discriminative stimulus in a majority of subjects. This study is the first report of successful training of a drug discrimination in rats using muscimol. Evidence is provided from substitution and antagonism testing with THIP and bicuculline, respectively, that the muscimol discrimination was mediated by actions at the GABA binding site on the GABAA receptor-ionophore complex. Results, also suggest that drug stimulus control by muscimol is weak compared to that of other types of GABA agonists previously studied using drug discrimination procedures in rodents.
...
PMID:The discriminative stimulus effects of muscimol in rats. 908 3


<< Previous 1 2 3 4 5 6 7 Next >>

---