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 role played by cholinergic activity in the effects of phencyclidine (PCP) on schedule-controlled responding was studied in three squirrel monkeys trained to respond on a variable-interval (VI) 100 sec schedule of food presentation. A low dose of PCP (0.08 mg/kg IM) produced small increases in rates of responding. Higher doses (0.16--0.64 mg/kg) produced dose-dependent decreases in rates of responding. Atropine (0.05--3.2 mg/kg IM) and physostigmine (0.025--0.20 mg/kg IM) caused only decreases in response rates, the dose-response curve for atropine being particularly flat over a wide range of doses. When atropine was combined with PCP, no significant interaction was obtained. When physostigmine was combined with PCP, a complex interaction was observed. Evidence fo partial antagonism of PCP by physostigmine was obtained only at the highest PCP dose tested. Atropine-physostigmine combinations resulted in response rates suggestive of antagonism.
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PMID:Effects of phencyclidine, atropine and physostigmine, alone and in combination, on variable-interval performance in the squirrel monkey. 11 14

Choice responding in a T-shaped maze has been made contingent upon whether or not rats experienced certain drug effects. The drug discriminative cues used in the present state-dependent (StD) model were those of phencyclidine (PCP) and ditran. The specificity of these cues and their possible drug inhibition and antagonism was studied. It was found that the lower the training dose used the slower the appearance of the drug discriminative formation. Transfer testings with ketamine and cyclohexamine showed that they were interchangeable with PCP. The order of their relative potency was: cyclohexamine greater than PCP greater than ketamine. Atropine transferred to ditran. Administration of compounds not structurally related to the training drugs did not show transfer. Pretreatment with parachlorphenylalanine (p-CPA) or tetrabenazine (TBZ) plus imipramine did not indicate inhibition or antagonism in PCP trained rats. Tacrine (THA) and especially physostigmine effectively antagonized the ditran-induced cues. Yohimbine and neostigmine did not.
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PMID:Drug discrimination in rats: the effects of phencyclidine and ditran. 12 31

The nerves of Latarjet and those going directly to the fundus and the body of the stomach were stimulated to determine their effect on gastric electrical control activity (ECA) and contractions. The lower limits of effective stimulation parameters were: pulse frequency 2 pulses per sec, pulse width 2 msec, pulse amplitude 0.3 ma or 5 v. Stimulation at or near the lower limits of stimulation parameters caused contractions with little effect on gastric ECA. At higher pulse repetition rates and amplitudes, vagal stimulation caused premature control potentials (PCP's), delayed control potentials (dcp's), and contractions throughout the electrically active region. The PCP's and DCP's in the antrum became phase-unlocked from those in the corpus. After 2 to 5 min of such vagal stimulation, PCP's and DCP's disappeared; gastric control waves became phase-locked at normal frequency and aboarad phase lag. Contractions continued to occur. Atropine and hexamethonium blocked all effects of vagal stimulation. After gastric ECA became insensitive to vagal stimulation, PCP's could still be produced by intraarterial acetylcholine or dimethylphenylpiperazinium, or by an electrical stimulus applied to gastric muscle, and physostigmine could temporarily restore ECA sensitivity to vagal stimulation. The ECA-insensitive state to vagal stimulation represents depletion of acetycholine at preganglionic sites.
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PMID:Vagal control of gastric electrical control activity and motility. 111 77

Phencyclidine (1-(1-phenylcyclohexyl)piperidine [PCP]), a behaviorally active analogue (1-(1-m-aminophenylcyclohexyl)piperidine [m-amino-PCP]), and two behaviorally inactive analogues (1-(1-m-nitrophenylcyclohexyl)piperidine and 1-piperidinocyclohexanecarbonitrile) block neuromuscular transmission, depress the amplitude and rate of rise of directly elicited action potentials in frog sartorius muscle, and cause voltage- and concentration-dependent decreases of the peak end-plate current amplitude. This implies that all four compounds block the ion channel of the acetylcholine (ACh) receptors. Only PCP and m-amino-PCP prolong the action potential, block delayed rectification, potentiate muscle twitch, increase quantal content of end-plate potentials, and block K+-induced 86Rb+ efflux from rat brain synaptosomes. PCP also possesses central and peripheral antimuscarinic activity but is much less potent than 3-quinuclidinyl benzilate (QNB). Atropine, scopolamine, and QNB require much higher concentrations to induce behavioral alterations than to block muscarinic receptors. Thus PCP and some of its behaviorally active and inactive derivatives share two common effects, blockade of the nicotinic ACh receptor-ion channel complex and blockade of central and peripheral muscarinic receptors. The feature that apparently separates behaviorally active from inactive derivatives of PCP is their ability to block K+ conductance (gK) and thereby potentiate muscle twitch and increase the release of transmitters from central and peripheral synapses. The similarity between PCP-induced behavioral alterations and primary schizophrenia in humans raises the possibility of involvement of an altered gK in the human disease.
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PMID:Interactions of phencyclidine with ion channels of nerve and muscle: behavioral implications. 630 62

Phencyclidine (PCP) has multifaceted actions on the cholinergic functions, including interaction with the central and peripheral cholinergic receptors. Therefore, to evaluate the possible involvement of the nicotinic and muscarinic acetylcholine (ACh) receptors during the behavioral toxicity of PCP, influence of various cholinergic modifiers on the PCP-induced behavioral effects in male Swiss mice was studied. PCP-induced (45 mumol/kg, IP) behavioral toxicity (circular movements, side-to-side head movements, and hyperactivity leading to convulsions) was blocked by pretreating the animals with secondary- or tertiaryamino -cholinergic modifiers, mecamylamine (ME; 14.9 and 29.9 mumol/kg), nicotine (NI; 12.3 and 30.8 mumol/kg) and physostigmine (PH; 0.16 and 0.31 mumol/kg). NI at 1.5 mumol/kg significantly potentiated the PCP-induced convulsions. Atropine (AT; 14.4 and 28.8 mumol/kg) pretreatments shortened the onset of circular movements. The locomotor activity of PCP (16.4 mumol/kg) was blocked by ME, NI, and PH. AT at 7.2 mumol/kg significantly potentiated the PCP-locomotion by 62%. These observations indicated that the behavioral actions of PCP, at least in part, are mediated by the central nicotinic and muscarinic ACh receptors. The involvement of cholinergic receptors in conjunction with the dopaminergic actions of PCP during these behaviors also has been discussed.
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PMID:Effects of mecamylamine, nicotine, atropine and physostigmine on the phencyclidine-induced behavioral toxicity. 672 72

Phencyclidine (PCP) administration in rats acutely in high doses or chronically in lower doses causes neurotoxicity characterized by neuronal vacuolization and apoptotic neuronal death, respectively. The purpose of this study was to determine whether drugs that previously had been reported to prevent either type of neurotoxicity were also able to prevent locomotor sensitization following chronic PCP administration. PCP (5 or 20 mg/kg) was administered once a day for 5 days following drug pretreatment. After withdrawal, rats were challenged with 3.2 mg/kg PCP and locomotor activity was assessed. Haloperidol and clozapine significantly attenuated sensitization elicited by PCP (20 mg/kg). The D(1)-like antagonist SCH23390 was much less effective than clozapine, showing a marginal inhibition. Risperidone, a D(2)/serotonin (5-HT(2)) antagonist, also resulted in a marginal attenuation of 15%. Ketanserin, a 5-HT(2) antagonist, had no effect. Atropine retarded sensitization by 35% and (+)-sulpiride caused a 50% reduction. The AMPA/kainate antagonist, 6,7-dinitroquinoxaline-2,3-dione, had no effect, but barbital sodium reduced sensitization by 54%. These data suggest that gamma-aminobutyric acid A, D(2), and muscarinic receptors play a major role in the complex pathway underlying sensitization to PCP, whereas D(1), 5-HT(2) and AMPA receptors have little or no relevance in the behavioral sensitization produced by 20 mg/kg PCP. In a model using 5 mg/kg PCP, the effects of sulpiride and SCH23390 replicated those observed with 20 mg/kg PCP and further showed that acute locomotor activation is not a strict requirement for the development of sensitization. These data argue that there is overlap, but nonidentity, between the mechanisms underlying PCP-induced sensitization and neurotoxicity.
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PMID:Pharmacological characterization of locomotor sensitization induced by chronic phencyclidine administration. 1118 23