The joint French-US seminar on phencyclidine and related arylcyclohexylamines

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25412/1/0000861.pd

Characterization of 'non-N-methyl-d-Aspartate' binding sites for gacyclidine enantiomers in the rat cerebellar and telencephalic structures

International audienc

Interaction of gacyclidine enantiomers with ‘non-NMDA’ binding sites in the rat central nervous system

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Binding properties of [3H]gacyclidine (cis(pip/me)-1-[1-(2-thienyl)-2-methylcyclohexyl]piperidine) enantiomers in the rat central nervous system

International audienc

Prenatal infection obliterates glutamate-related protection against free hydroxyl radicals in neonatal rat brain

International audienc

Re-evaluation of phencyclidine low-affinity or ?non-NMDA? binding sites

International audienc

Binding properties of 3-[125I]iodophencyclidine, a new radioligand for N-methyl-D-aspartate-gated ionic channels.

International audienceThe binding properties of the 125I-labeled phencyclidine derivative N-[1-(3-[125I]iodophenyl)cyclohexyl]piperidine (3-[125I]iodo-PCP), a new ligand of the N-methyl-D-aspartate (NMDA)-gated ionic channel, were investigated. Association and dissociation kinetic curves of 3-[125I]iodo-PCP with rat brain homogenates were well described by two components. About 32% of the binding was of fast association and fast dissociation, and the remaining binding was of slow association and slow dissociation. Saturation curves of 3-[125I]iodo-PCP also were well described using two binding sites: one of a high affinity (KDH = 15.8 +/- 2.3 nM) and the other of a low affinity (KDL = 250 +/- 40 nM). 3-Iodo-PCP inhibited the binding of 3-[125I]iodo-PCP with inhibition curves that were well fitted by a two-site model. The binding constants (KiH, BmaxH; KiL, BmaxL) so obtained were close to those obtained in saturation experiments. Ligands of NMDA-gated ionic channels also inhibited the binding of 3-[125I]iodo-PCP with two constants, KiH and KiL. There was a very good correlation (r = 0.987) between the affinities of these ligands to bind to NMDA-gated ionic channels and their potencies to inhibit the binding of 3-[125I]iodo-PCP with a high affinity. Moreover, the regional distribution of the high-affinity binding of 3-[125I]-iodo-PCP paralleled that of tritiated N-[1-(2-thienyl)cyclohexyl]piperidine ([3H]TCP). In contrast to that of [3H] TCP, the binding of 3-[125I]iodo-PCP to well-washed rat brain membranes was fast and insensitive to glutamate and glycine.(ABSTRACT TRUNCATED AT 250 WORDS

Inhibition of locus coeruleus neurons by the phencyclidine analog, N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine: evidence for potent indirect adrenoceptor agonist properties

International audienceThe effects of the phencyclidine derivative, N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine (BTCP), on the electrical activity of noradrenaline (NA) neurons of the locus coeruleus (LC) were studied in halothane-anesthetized rats. Systemic administration of BTCP potently inhibited LC neurons (ID50 of 1.1 +/- 0.1 mg/kg i.v.). This effect was mimicked by local microejection of BTCP into the LC. Both the systemic and local effects of BTCP were blocked by alpha 2-adrenoceptor antagonists and prevented by prior depletion of catecholamines with reserpine. These and other data suggest that BTCP behaves as a potent indirect NA agonist (i.e. via NA re-uptake and/or release systems)