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 high pressure neurological syndrome (HPNS) occurs when man or animals are exposed to hyperbaric pressure. Four non-competitive N-methyl-D-aspartate (NMDA) antagonists - MK-801, phencyclidine (PCP), SKF 10,047 and ketamine were tested in rats for effects on the HPNS. All drugs were injected i.p. prior to compression; ketamine was also infused i.v. Control rats received saline. Rats were exposed individually to increasing helium pressure (PO2 0.5 atmospheres absolute ATA). Three endpoints were used to assess HPNS: onset pressures for tremor, myoclonus and convulsions. Neither MK-801 (0.03 and 0.3 mg/kg) nor SKF 10,047 (50 mg/kg) had any effect on the onset pressures for tremor, myoclonus or convulsions, although the type of seizure was modified from the clonic/tonic seizure seen in controls to purely clonic. PCP (5 mg/kg) had no effect on the endpoints, but pressure enhanced the excitation and stereotypy seen at 1 ATA. Ketamine (100 mg/kg i.p.) did not affect tremor or myoclonus; ketamine infused i.v. at pressure only prevented tremor and myoclonus at 'anaesthetizing' concentrations. Our results show that these non-competitive NMDA antagonists had little effect on HPNS, in contrast to competitive NMDA antagonists, such as AP7, which are highly effective. Possible explanations for this lack of effect include (1) interactions with NMDA receptor channels are pressure dependent; (2) other actions of these antagonists override their effects on the NMDA receptor channel.
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PMID:The effects of non-competitive NMDA receptor antagonists on rats exposed to hyperbaric pressure. 254 78

Chronic treatment with low doses (1-2 mg/kg) of phencyclidine (PCP) produces marked behavioral effects in the developing kitten. These effects are age-dependent. Under 21 days the major response consists of rostrocaudal forelimb movements. After this age the major responses are ataxic locomotion and waxy rigidity. In the present experiment the behavioral effect of subcutaneous injections of higher doses of PCP, two of its metabolites, phencylclohexylamine (PCA) and an alcohol (N-(5-hydroxypentyl)-1-phenycyclohexylamine) (AL) and one PCP analog (N-N-diethylaminophenylhexylamine (NND] were tested in kittens between 30-50 days of age. The behavior of the kittens was assessed from 10-15 min pre-injection to up to 5 hr postinjection and at 24 hr postinjection. The most intense responses were produced by PCP and NND and consisted of waxy rigidity (limbs in abnormal postures for extended time periods) with the animal completely immobile. PCA was less effective, producing only tremor and staggering followed by loss of hindlimb support. AL was the least effective producing minimal behavioral responses. These results indicate that some of the metabolites of PCP, while active, are not as potent as PCP itself. Subsequent testing indicated that behavioral tolerance to the effects of PCP, NND and PCA occurred after a single administration of these compounds.
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PMID:Behavioral effects of phencyclidine and some of its metabolites in developing cats. 376 62

This study was designed to assess the sex differences in phencyclidine(PCP)-induced ambulatory activity in an open-field, stereotyped behaviors, motor incoordination, tremor, salivation, the regional and subcellular distributions of PCP in the brain and the half-life of PCP in the brain and plasma. Female rats appeared to be more sensitive to PCP as evidenced by hyperactivity, stereotyped behaviors, motor incoordination, tremor, salivation and ataxia. The concentrations of PCP in female rat brain were higher than in the male rats in some discrete brain areas and subcellular fractions. The half-life of PCP in the brain and plasma was longer in female rats than in male rats. The inverse relationship of pharmacological responses to PCP and biotransformation of PCP in both sexes of rats suggests that sex differences in pharmacological actions of PCP depend largely on differences in ability to biotransform the drug.
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PMID:Sex-dependent differences in the pharmacological actions and pharmacokinetics of phencyclidine in rats. 653 6

The non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists phencyclidine (PCP) and dizocilpine maleate (MK801) cause nystagmus, tremor, and cerebellar ataxia at toxic doses. We have shown that PCP but not MK801 is toxic to rat cerebellar Purkinje cells. To study the mechanism and pathways of PCP and MK801 action, Fos protein expression was examined in the cerebellum and functionally related nuclei of the brainstem. PCP, 1-50 mg/kg i.p., induced Fos immunostaining in neurons of the inferior olive, cerebellar granule cell layer, and deep cerebellar and vestibular nuclei. At higher doses, PCP, 25-50 mg/kg, induced dense Fos immunoreactivity throughout the inferior olive except for rostral parts of medial accessory olive and caudal parts of principal olive. At lower doses of PCP, 1-10 mg/kg, Fos positive cells in inferior olive were concentrated in the subnucleus beta. In the cerebellum Fos positive granule cells were arranged in patches distributed throughout the cerebellar cortex following PCP, 1-50 mg/kg. Rare Fos positive Purkinje cells were observed adjacent to these patches. At the highest dose of PCP tested (50 mg/kg), Fos was expressed in the fastigial, interpositus, and dentate nuclei, and in vestibular nuclei, most prominently in the medial vestibular nucleus. At lower doses, Fos was expressed mainly in medial cerebellar output nuclei and in vestibular nuclei. MK801, 0.2-10 mg/kg i.p., induced Fos expression in the same regions as PCP. However, MK801-induced Fos expression in inferior olive was localized primarily to subnucleus beta. No apparent differences in the number or distribution of Fos positive neurons were observed at MK801 doses of 0.2-10 mg/kg. MK801 also induced Fos expression in fastigial and vestibular nuclei, but not in lateral (interpositus and dentate) cerebellar nuclei. MK801, 0.2-10 mg/kg, induced patchy Fos expression in cerebellar granule cells that was similar to PCP. These results support our earlier observations that PCP and MK801 have different actions in the cerebellum, although they both cause ataxia and indistinguishable behavioral symptoms. That high doses of PCP induce substantially more Fos expression in inferior olive than MK801 suggests that its toxicity to Purkinje cells is at least partially the result of excessive activity of climbing fibers, the excitatory neural input that arises from the inferior olive and synapses on Purkinje cell dentrities.
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PMID:FOS expression in the brainstem and cerebellum following phencyclidine and MK801. 882 Sep 68

Four major components of the mechanism of action have been identified for the antiparkinsonian drug budipine up to now. 1) The primary action of budipine is an indirect dopaminergic effect as shown by facilitation of dopamine (DA) release, inhibition of monoamine oxidase type B (MAO-B) and of DA (re) up-take and stimulation of aromatic L-amino acid decarboxylase (AADC), which in sum might be responsible for enhancing the endogenous dopaminergic activity. 2) Radioligand and functional studies at the N-methyl-D-aspartate (NMDA) type glutamate receptor characterize budipine as a low-affinity, uncompetitive antagonist with fast kinetics and moderate voltage-dependency at the phencyclidine (PCP) binding site, comparable to that observed with amantadine, thereby counteracting an increased excitatory glutamatergic activity. 3) The antimuscarinic action of budipine, verified by functional and binding studies at native muscarinic M1-M3 and human recombinant m1-m5 receptor subtypes in vitro, is up to 125-fold weaker than that of biperiden and corresponds to its approximately 100-fold lower potency to cause experimentally-induced peripheral antimuscarinic effects and explains only part of its high potency, which equals biperiden, to suppress cholinergically evoked tremor. 4) An additional inhibition of striatal gamma-aminobutyric acid (GABA) release by budipine may be beneficial to suppress an increased striatal GABAergic output activity. The contribution of other observed effects to the therapeutic action of budipine, i.e. weak stimulation of noradrenaline and serotonin release, binding to brain sigma1 receptors and blockade of histamine H1 receptors, is not yet clear. By means of these multiple mechanisms, budipine might correct the imbalance of striatal output pathways by restoring DA levels in the striatum, and positively influence the secondary changes in other transmitter systems (glutamate, acetylcholine, GABA) observed in Parkinson's disease.
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PMID:Multiple mechanisms of action: the pharmacological profile of budipine. 1037 Sep 4