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)

Repeated exposure to psychomotor stimulants produces long-lasting molecular, cellular and locomotor behavioral changes. Such changes are likely to contribute to the development of drug addiction and psychosis. It is not clear whether these durable changes are accompanied by lasting changes in cognition. We examined the long-term effects of repeated treatment with phencyclidine (PCP) or amphetamine on working memory, using a discrete, paired-trials, delayed-alternation task sensitive to the acute effects of PCP and amphetamine, and to the integrity of the prefrontal cortex. Twice daily treatment with PCP (5.0 mg/kg) or amphetamine (2.5 mg/kg) for 5 days did not produce lasting, significant impairments in alternation performance in comparison to either pre-treatment baseline performance or to the vehicle-treated group. Subsequent challenge doses of PCP (1, 3 and 5 mg/kg) produced alternation deficits in vehicle, PCP, and amphetamine pre-treated groups that were dependent on dose, but not on pre-treatment regimen. However, rats pre-treated with PCP showed a trend towards sensitization in response to PCP challenge. The present data suggest that psychostimulant treatment regimens that are reported to produce long-lasting changes in neural morphology and locomotor behavior may not produce equally durable changes in working memory.
 ...
PMID:Effects of repeated treatment with amphetamine or phencyclidine on working memory in the rat. 1219 13

Chemical substance abuse has tormented mankind throughout history. A number of chemical approaches have been employed in an attempt to treat chemical addiction. Unfortunately, most of these have proven unsuccessful though several chemical entities have been shown to be moderately effective. The naturally occurring alkaloid ibogaine has been reported to interrupt the cravings for alcohol, cocaine and opiates. Other alkaloids from Tabernanthe iboga, such as ibogamine and tabernanthine, provide insight into the structure activity relationship at the different receptors believed to be involved in addiction. The synthetic iboga alkaloid congener, 18-MC, also shows potential as an anti-addictive agent without the hallucinogenic effects of ibogaine. Additionally, acamprosate, BP 897, GBR12909, lofexidine and memantine have shown promising results in the treatment of addiction. All of these leads provide a start for the medicinal chemist to design anti-addictive agents, since currently no drugs are approved in the U.S. for the treatment of addictions to cocaine, methamphetamine, other stimulants or PCP.
 ...
PMID:A review of chemical agents in the pharmacotherapy of addiction. 1236 79

Substance abuse remains a complex and pervasive conundrum for society and for clinicians seeking to improve the lives of their pediatric patients. Substance abuse is linked to the human instinct for pleasure at any cost and is fueled by enticing encouragement of the media teaching society to seek drug-induced pleasure without fear of negative consequences. Other complications are the limited education about psychoactive substances provided to youth and the health care profession pledged to serve them. Primary care clinicians must provide their adolescent patients with adequate screening and counseling about substance abuse. Treatment of the substance-abusing patient is often a combination of behavioral interventions (including family therapy), and, in limited situations, addiction-specific medications. Research suggests that female drug addicts have a better outcome in female-only drug treatment programs. In addition, new drugs are being developed that target specific brain mechanisms involved in drug addiction; these drugs will have less toxicity and less abuse potential than illicit drugs such as cocaine. Vaccines are being developed that will block the effects of such drugs as cocaine and PCP. Medications developed for the treatment of depression and epilepsy will be a source of medications for the treatment of drug addiction. The study of endorphins and the neurobiology of stress and substance abuse promise to develop potent anti-addiction chemicals, greatly aiding in the war on drug abuse.
 ...
PMID:Substance abuse in adolescents: a complex conundrum for the clinician. 1455 85

N-methyl-D-aspartate (NMDA) receptors, a subtype of glutamate receptors (GluRs) formed by assembly of the GluRzeta subunit (called NR1 in rats) with any one of four GluRepsilon subunits (GluRepsilon1-4; NR2A-D), play an important role in excitatory neurotransmission, synaptic plasticity and brain development. Recent pharmacological studies have also indicated a role for NMDA receptors in drug addiction. In the present study, we investigated the behavioural adaptations to addictive drugs such as phencyclidine (PCP), methamphetamine (MAP) and morphine (MOR) in mice lacking the GluRepsilon1 subunit of the NMDA receptor. GluRepsilon1 mutant mice exhibited a malfunction of NMDA receptors, as evidenced by the reduction of [3H]MK-801 binding in an autoradiographic receptor binding assay. GluRepsilon1 mutant mice showed an attenuation of acute PCP- and MAP-induced hyperlocomotion. The development of sensitization by repeated treatment with PCP and MAP at a low, but not high, dose was also suppressed. The development of MOR-induced analgesic tolerance and naloxone-precipitated MOR withdrawal symptoms were attenuated in GluRepsilon1 mutant mice. In the place conditioning test, PCP-induced place aversion in naive mice and place preference in PCP-pretreated mice, as well as MOR-induced place preference, were diminished whereas MAP-induced place preference was not affected in GluRepsilon1 mutant mice. These findings provide genetic evidence that GluRepsilon1 subunit-containing NMDA receptors are involved in certain aspects of drug addiction.
 ...
PMID:Behavioural adaptations to addictive drugs in mice lacking the NMDA receptor epsilon1 subunit. 1475 Sep 73

Drug addiction is a major worldwide medical and social problem that continues to escalate. The addiction syndrome is remarkably similar between different drugs of abuse, and can be characterized as a chronic relapsing brain disorder with neurobiological changes that lead to a compulsion to take a drug with loss of control over drug intake. Presently used medications for the treatment of dependence disorders are based on drugs that are either agonists or antagonists of drugs of abuse, and have yielded only limited success. Immunopharmacotherapy is based on the generation or administration of antibodies that are capable of binding the targeted drug before it can reach the brain, whereas replacement strategies based on agonists or antagonists of these drugs generally cause many undesired side effects. A large amount of data has been gathered in recent years on the effects of active and passive immunization against cocaine, nicotine, PCP and methamphetamine in animal models, suggesting potential efficacy of these treatments in humans; and clinical trials are currently underway for vaccines against cocaine and nicotine.
 ...
PMID:Development of immunopharmacotherapy against drugs of abuse. 1647 21

The sigma-1 receptor is a unique non-opioid, non-PCP binding site that has been implicated in many different pathophysiological conditions including psychosis, drug addiction, retinal degeneration and cancer. Based on the structure of fenpropimorph, a high affinity (K(i)=0.005 nM)(1) sigma-1 receptor ligand and strong inhibitor of the yeast sterol isomerase (ERG2), we previously deduced a basic sigma-1 receptor pharmacophore or chemical backbone composed of a phenyl ring attached to a di-substituted nitrogen atom via an alkyl chain.(2) Here, we report the design and synthesis of various N,N-dialkyl or N-alkyl-N-aralkyl derivatives based on this pharmacophore as well as their binding affinities to the sigma-1 receptor. We introduce three high affinity sigma-1 receptor compounds, N,N-dibutyl-3-(4-fluorophenyl)propylamine (9), N,N-dibutyl-3-(4-nitrophenyl)propylamine (3), and N-propyl-N'-4-aminophenylethyl-3-(4-nitrophenyl)propylamine (20) with K(i) values of 17.7 nM, 0.36 nM, and 6 nM, respectively. In addition to sigma receptor affinity, we show through cytotoxicity assays that growth inhibition of various tumor cell lines occurs with our high affinity N,N-dialkyl or N-alkyl-N-aralkyl derivatives.
 ...
PMID:Synthesis and characterization of N,N-dialkyl and N-alkyl-N-aralkyl fenpropimorph-derived compounds as high affinity ligands for sigma receptors. 2049 18

In this paper, we have outlined the neurobiological basis of alcohol and drug dependence. The prevalence of drug dependence is a serious social problem in many countries, including Japan. This problem involves many background factors, including those pertaining to medical sciences, socio economics, and politics. First, we briefly describe the findings pertaining to psychotomimetic drugs as a model of schizophrenia. The biological pathogenesis of schizophrenic disorders is still unknown. The symptoms of methamphetamine (MAP) and phencyclidine (PCP) psychoses are very similar to those of schizophrenic disorders involving hallucination or delusion. PCP causes not only positive symptoms but also negative symptoms. Therefore, it has been considered as a more comprehensive model of schizophrenia than other drugs. Furthermore, amotivational syndrome, which is observed in patients with chronic cannabis and organic solvent dependence, is similar to the negative symptoms of schizophrenia. Understanding the neurobiological basis of drug dependence by using the molecular biological approach will provide an important clue for elucidating the mechanisms underlying schizophrenia and endogenous psychiatric disorders. Next, we discuss account for the neurobiological mechanisms underlying drug dependence. The reward system in the brain, which is common for all dependent drugs, has been explained, and the stages of addiction corresponding to the development of drug dependence have been discussed followed. In addition, we have discussed the epigenetics aspects of substance dependence, which is one of the hottest topics in psychiatric genetics. We expect that further studies of the mechanisms underlying drug dependence will aid in elucidating of the pathophysiology of various psychiatric diseases.
 ...
PMID:[Alcohol and substance dependence]. 2230 61

N-Methyl-d-aspartate (NMDA) receptor dysfunction has been linked to several neuropsychiatric disorders, including Alzheimer's disease, epilepsy, drug addiction, and schizophrenia. A radioligand that could be used with PET to image and quantify human brain NMDA receptors in the activated "open channel" state would be useful for research on such disorders and for the development of novel therapies. To date, no radioligands have shown well-validated efficacy for imaging NMDA receptors in human subjects. In order to discover improved radioligands for PET imaging, we explored structure-affinity relationships in N'-3-(trifluoromethyl)phenyl derivatives of N-aryl-N'-methylguanidines, seeking high affinity and moderate lipophilicity, plus necessary amenability for labeling with a positron-emitter, either carbon-11 or fluorine-18. Among a diverse set of 80 prepared N'-3-(trifluoromethyl)phenyl derivatives, four of these compounds (13, 19, 20, and 36) displayed desirable low nanomolar affinity for inhibition of [(3)H](+)-MK801 at the PCP binding site and are of interest for candidate PET radioligand development.
...
PMID:N'-3-(Trifluoromethyl)phenyl Derivatives of N-Aryl-N'-methylguanidines as Prospective PET Radioligands for the Open Channel of the N-Methyl-d-aspartate (NMDA) Receptor: Synthesis and Structure-Affinity Relationships. 2658 60

New psychoactive substances (NPSs) have become an integral part of the recreational drug market with "new" compounds being reported by the European Monitoring Centre for Drugs and Drug Addiction weekly. Due to the changing nature of NPSs, it is impractical to carry out single analyte or even simple class quantitation. Although several gas chromatography-mass spectrometry (GC-MS) methods have been developed these are typically class specific. We present a validated GC-MS method for the quantitation of 2-DPMP, 3-MeO-PCE, 3-MeO-PCP, 5-APB, 6-APB, benzedrone, butylone, ethylone, flephedrone, methiopropamine, MDPV, mephedrone, methoxetamine, methylone, naphyrone, 25B-NBOME, 25C-NBOME, 25D-NBOMe, 25E-NBOME, 25H-NBOME, 25I-NBOME, Mescaline-NBOME and 25P-NBOME in blood and urine samples. Sample preparation was carried out using solid-phase extraction followed by derivatisation and analysis by GC-MS. Parameters investigated for validation included bias, precision, linear calibration model, carryover, interferences, limit of detection, limit of quantification, and autosampler and freeze/thaw stability. All drugs yielded successful results for each of these parameters as per SWGTOX guidelines. The GC-MS method was used for the reanalysis of 12 blood samples (eight cases) where 25I-NBOMe, 25C-NBOMe, methoxetamine and methylone had previously been detected by NMS laboratories. This GC-MS method was able to quantitatively detect these drugs in 75% of the blood samples, 42% of which contained either 25C-NBOMe or 25I-NBOMe. This method accurately allows for the simultaneous quantification of a wide variety of compounds via GC-MS, in particular NBOMe compounds which are typically analysed by liquid chromatography-tandem mass spectrometry which is not available in all laboratories.
 ...
PMID:Gas Chromatography-Mass Spectrometry Method for the Quantitative Identification of 23 New Psychoactive Substances in Blood and Urine. 3069 23