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The Journal of Pharmacology and... Jul 1984A series of phencyclidine (PCP) related analogs, carbonitrile synthetic precursors and two monohydroxylated metabolites were compared pharmacologically in mice for their...
A series of phencyclidine (PCP) related analogs, carbonitrile synthetic precursors and two monohydroxylated metabolites were compared pharmacologically in mice for their ability to produce ataxia using the rotarod method and toxicologically for their acute 4-hr lethality. The slope of the PCP dose-ataxic response curve was steeper than those of diazepam, pentobarbital, morphine and ketocyclazocine but not the slope of the sigma agonist, N-allylnormetazocine curve. Responses for all analogs, metabolites and precursors produced curves parallel to that of PCP. Ataxia potencies of all PCP-related compounds ranged from 0.05 to 2.15 X PCP and durations of action ranged from 18 to 65 min. N-ethyl-1-phenylcyclohexylamine, 1-[1-(2-thienyl)-cyclohexyl]-piperidine and 1-[1-(2-thienyl)-cyclohexyl]-pyrrolidine were most potent and least potent were 1-(1-phenyl-cyclohexyl)-4-methylpiperidine, the phenyl and thienyl morpholines and 4-phenyl-4-piperidinocyclohexanol. Among the PCP analogs, modifying the piperidine or aromatic ring effected changes only in potency. Seizures and respiratory depression characterized the lethal effects of PCP, its analogs, metabolites and precursors. However, the precursors failed to elicit the stereotyped movements and hyperactivity that preceded seizures produced by the other compounds. Overall potencies for lethality relative to PCP covered a narrow range (0.16-1.83) with the carbonitrile precursors being most potent. Therapeutic indices indicated relatively large margins of safety for 1-[1-(2-thienyl)-cyclohexyl]-piperidine, 1-[1-(2-thienyl)-cyclohexyl]-piperidine, N-ethyl-1-phenylcyclohexylamine and ketamine and the smallest were for 1-(1-phenylcyclohexyl)-4-methylpiperidine, the metabolite 4-phenyl-4-piperidinocyclohexanol and the three precursors.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Animals; Ataxia; Lethal Dose 50; Male; Mice; Motor Activity; Phencyclidine; Time Factors
PubMed: 6747825
DOI: No ID Found -
Journal of Analytical Toxicology 1980Following intraperitoneal injection of phencyclidine in the rat, concentrations ranged from 148 to 1364 ng/mL in saliva (mean +/- SD, 567 +/- 415) and from 196 to 1016...
Following intraperitoneal injection of phencyclidine in the rat, concentrations ranged from 148 to 1364 ng/mL in saliva (mean +/- SD, 567 +/- 415) and from 196 to 1016 ng/mL in corresponding serum samples (mean +/- SD, 502 +/- 231). Phencyclidine concentrations in saliva showed no significant correlation with those in serum, and saliva concentrations were occasionally higher than serum concentrations. The saliva:serum concentration ratios ranged from 0.4 to 3.0. Since hypersalivation is common in man and animals after phencyclidine ingestion, measurement of the compound in saliva may provide a useful alternative to serum and urine which are not always available for analysis.
Topics: Animals; Chromatography, Gas; Female; Phencyclidine; Rats; Saliva
PubMed: 7206661
DOI: 10.1093/jat/4.6.311 -
Journal of Forensic Sciences Oct 1980
Topics: Cross Reactions; Immune Sera; Phencyclidine; Radioimmunoassay
PubMed: 7430984
DOI: No ID Found -
Alaska Medicine Jan 1979
Topics: Adolescent; Behavior; Diagnosis, Differential; Humans; Illicit Drugs; Male; Mental Disorders; Phencyclidine; Prognosis; Substance-Related Disorders
PubMed: 426236
DOI: No ID Found -
Journal of Medicinal Chemistry May 1981Several esters of 1-(1-phenylcyclohexyl)-4-piperidinol (3), 1-(1-phenylcyclohexyl)-4-phenyl-4-piperidinol (10) and its propionate (11), and...
Several esters of 1-(1-phenylcyclohexyl)-4-piperidinol (3), 1-(1-phenylcyclohexyl)-4-phenyl-4-piperidinol (10) and its propionate (11), and 1-(1-phenylcyclohexyl)-4-phenylpiperidine (13) were prepared and characterized. The new compounds, which are derived from phencyclidine, exerted analgesic activity in mice. The most potent is 10, which is twice as active as morphine. The antinociceptive activity of 10, 11, and 13 could be well correlated with their potency in the mouse vas deferens bioassay, and both were completely reversed by naloxone.
Topics: Analgesics; Animals; Chemical Phenomena; Chemistry; Lethal Dose 50; Male; Mice; Motor Activity; Phencyclidine; Reaction Time
PubMed: 7241506
DOI: 10.1021/jm00137a004 -
The American Journal of Psychiatry Apr 1983The epidemic abuse of phencyclidine (PCP) has become a major psychiatric issue within the past decade. With the assistance of highly sensitive capillary gas...
The epidemic abuse of phencyclidine (PCP) has become a major psychiatric issue within the past decade. With the assistance of highly sensitive capillary gas chromatographic-nitrogen detector measurements, PCP's true pervasiveness is only now being appreciated. To further quantitate the severity of the problem, the authors analyzed samples of umbilical cord blood from 200 patients on the obstetrics service of a major university medical center. Preliminary results revealed that 24 (12%) of the samples were positive for PCP (.10-5.80 ng/ml). The authors discuss the significance of this finding with regard to psychiatry, obstetrics, pediatrics, and juvenile law.
Topics: Child Abuse; Female; Fetal Blood; Humans; Infant, Newborn; Infant, Newborn, Diseases; Maternal-Fetal Exchange; Phencyclidine; Pregnancy; Substance-Related Disorders; United States
PubMed: 6837783
DOI: 10.1176/ajp.140.4.450 -
Pharmacology, Biochemistry, and Behavior Apr 1990Phencyclidine (PCP) pharmacokinetics and drug discrimination were examined in pigeons (n = 6 in both groups) after intramuscular doses of 1.48 mg/kg. PCP absorption was...
Phencyclidine (PCP) pharmacokinetics and drug discrimination were examined in pigeons (n = 6 in both groups) after intramuscular doses of 1.48 mg/kg. PCP absorption was rapid with maximum measured plasma concentrations ranging from 559 to 1450 ng/ml at 10-30 min after dosing, which corresponded to the time of maximum PCP stimulus effects in the drug discrimination studies. The terminal elimination half-life was 0.88 hr (harmonic mean). Average values for the volume of distribution and total body clearance were 1.6 l/kg and 18.2 ml/min/kg, respectively. In the behavioral studies, pigeons discriminated PCP-like effects from about 2 min to 2 hr after dosing. An average value for response on the PCP-appropriate key and for PCP concentration at each time point from 2 min to 2 hr was calculated from the individual subject data. Least-squares linear regression analysis of these data showed a highly significant relationship between the ability to discriminate PCP and log PCP concentration (y = 103x - 219, r2 = .810, p less than 0.005). This analysis suggests PCP concentration is a good predictor of behavioral efficacy.
Topics: Animals; Behavior, Animal; Columbidae; Discrimination, Psychological; Dose-Response Relationship, Drug; Injections, Intramuscular; Male; Phencyclidine
PubMed: 2345758
DOI: 10.1016/0091-3057(90)90361-k -
British Journal of Pharmacology Feb 1982The effects of N-(1-phenylcyclohexyl) piperidine (PCP) and related drugs on isolated intact segments of the guinea-pig ileum were determined. 1-1-(2-Thienyl)...
The effects of N-(1-phenylcyclohexyl) piperidine (PCP) and related drugs on isolated intact segments of the guinea-pig ileum were determined. 1-1-(2-Thienyl) cyclohexylpiperidine (TCP), PCP and ketamine decreased the height of electrically induced contractions (0.1 Hz) of intact segments of isolated guinea-pig ileum. Thirty to forty percent of the inhibition of contraction height (0.1 Hz) was reversed by pretreatment with the pure narcotic antagonist, naloxone. This naloxone-reversible component showed cross-tolerance with morphine. PCP pretreatment caused a shift to the right in the dose-response curve to acetylcholine (ACh) that was not parallel with the control dose-response curve. Thus PCP does not interact with the muscarinic cholinoceptor in a strictly atropine-like competitive fashion. Binding sites for [3H]-PCP were detected in homogenates of the guinea-pig longitudinal muscle-myenteric plexus preparation. The affinity constants and the rank order of potencies of various PCP derivatives competing with [3H]-PCP for binding suggest that these binding sites are very similar to those found in the central nervous system. These data suggest that the guinea-pig isolated ileum may be used as an in vitro system for studying the mechanism of action of phencyclidines.
Topics: Acetylcholine; Animals; Dihydromorphine; Dose-Response Relationship, Drug; Guinea Pigs; Ileum; In Vitro Techniques; Intestines; Male; Naloxone; Neurons; Phencyclidine; Receptors, Neurotransmitter; Receptors, Phencyclidine
PubMed: 6313107
DOI: 10.1111/j.1476-5381.1982.tb08782.x -
Annals of the New York Academy of... Feb 2012There are numerous medicinal chemistry reports in the literature describing the pharmacological properties of thousands of narcotics, stimulants, hallucinogens,... (Review)
Review
There are numerous medicinal chemistry reports in the literature describing the pharmacological properties of thousands of narcotics, stimulants, hallucinogens, sedative-hypnotic drugs, cannabinoids, and other psychoactive substances as well as synthetic methods for their preparations. This information, while essential for the advancement of science, has been used by clandestine chemists to manufacture and market an endless variety of analogs of so-called designer drugs. In this review, we describe how clandestine chemists used the principles of medicinal chemistry to design molecules, referred to as designer drugs, that elicit the effects of opioids, amphetamine and analogs, cannabinoids, and phencyclidine analogs while circumventing the law.
Topics: Amphetamines; Analgesics, Opioid; Animals; Cannabinoids; Chemistry, Pharmaceutical; Designer Drugs; Drug Design; Drug and Narcotic Control; Humans; Illicit Drugs; Phencyclidine; Scientific Misconduct; United States
PubMed: 22092008
DOI: 10.1111/j.1749-6632.2011.06199.x -
Sudebno-meditsinskaia Ekspertiza 1999Reviews data on analysis of narcotic phencyclidine and its main metabolites and analogs. Pharmacological and toxic characteristics of phencyclidine, conditions of its... (Review)
Review
Reviews data on analysis of narcotic phencyclidine and its main metabolites and analogs. Pharmacological and toxic characteristics of phencyclidine, conditions of its isolation from biological objects and its detection and measurement by thin layer and gas chromatography and by chromatographic mass-spectrometry are described. Analysis of phencyclidine metabolites is discussed and a scheme of its metabolism is presented. Statistical characteristics of methods of quantitative analysis of phencyclidine in biological objects are presented.
Topics: Animals; Body Fluids; Chromatography, Gas; Chromatography, Thin Layer; Gas Chromatography-Mass Spectrometry; Hallucinogens; Humans; Hydrogen-Ion Concentration; Phencyclidine; Solutions
PubMed: 10224923
DOI: No ID Found