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)

Experiments were conducted in order to examine the mechanism of changes in body temperature induced by phencyclidine (PCP) in mice. It is well known that morphine changes body temperature in a biphasic manner. PCP also produced hyperthermia at low doses (5 and 10 mg/kg) and hypothermia at high dose (40 mg/kg). The changes in body temperature induced by PCP were blocked by naloxone, a mu antagonist. Pretreatment with morphine (2.5 mg/kg), a mu agonist, or ethylketocyclazocine (EKC: 2.5 mg/kg), a kappa agonist, potentiated hypothermia induced by high dose of PCP. Effects of morphine and EKC on PCP-induced hypothermia were antagonized by naloxone. N-Allylnormetazocine (SKF 10 047: 20 mg/kg), a kappa and mu antagonist, antagonized PCP- and EKC + PCP-induced hypothermia but not morphine + PCP-induced hypothermia. Furthermore, Mr 2266, a kappa antagonist, antagonized PCP (10mg/kg)-induced hyperthermia and EKC + PCP-induced hypothermia. It is suggested that PCP may affect thermoregulation through mu and/or kappa opioid receptor mechanisms.
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PMID:Involvement of opioid receptors in hypo- and hyperthermic effects induced by phencyclidine in mice. 302 Feb 23

The enantiomeric (-)- and (+)-N-(methyl through decyl) normetazocines (5,9 alpha-dimethyl-2'-hydroxy-6,7-benzomorphans) were synthesized and their in vitro and in vivo activities determined. Increasingly bulky enantiomeric N-alkyl homologs were prepared until their interaction with the sigma 1 receptor decreased and their insolubility became a hindrance to their evaluation in vivo and/or in vitro. The (-)-methyl, -pentyl, -hexyl, and -heptyl homologs were essentially as potent as, or more potent than, morphine in the tail-flick, phenylquinone, and hot-plate assays for antinociceptive activity; the (-)-propyl homolog had narcotic antagonist activity between that of nalorphine and naloxone in the tail-flick vs morphine assay, and it also displayed antagonist properties in the single-dose suppression assay in the rhesus monkey. The antinociceptively potent (-)-heptyl homolog did not substitute for morphine in monkeys but did show morphine-like properties in a primary physical-dependence study in continuously infused rats. All five potent compounds showed high affinity for the mu opioid receptor from both rat and monkey preparations and the kappa opioid receptor (< 0.05 microM), and all except the (-)-methyl homolog interacted reasonably well at the delta receptor (K(i) < 0.1 microM). The (-)-propyl compound was equipotent (K(i) 1.5-2.0 nM) at mu and kappa receptors. The pattern of interaction of the (-)-enantiomeric homologs with mu receptors from rat and monkey preparations was similar, but not identical. The enantioselectivity of the homologs for mu receptors was greater in the rat than in the monkey preparation for all but the N-H and butyl compounds, and the enantioselectivity of the lower homologs (methyl through butyl) for the mu (monkey) receptor was greater than for the kappa or delta receptors. However, bulkier homologs (hexyl through decyl) displayed higher enantioselectivity at kappa or delta receptors than at the mu (monkey) receptor. The (+)-butyl through (+)-octyl homologs were essentially equipotent with, or more potent than, (+)-pentazocine at the sigma receptor. Only the (+)-H and (+)-methyl homologs had high affinity (< 0.05 microM) at PCP binding sites.
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PMID:Antipodal alpha-N-(methyl through decyl)-N-normetazocines (5,9 alpha-dimethyl-2'-hydroxy-6,7-benzomorphans): in vitro and in vivo properties. 793 69