Re‐evaluation of phencyclidine low‐affinity or “non‐NMDA” binding sites

  title={Re‐evaluation of phencyclidine low‐affinity or “non‐NMDA” binding sites},
  author={H{\'e}l{\`e}ne Hirbec and A L Mausset and Jean Marc Kamenka and Alain Privat and Jacques Vignon},
  journal={Journal of Neuroscience Research},
TCP and its derivative gacyclidine (± GK11) are high‐affinity non‐competitive antagonists of N‐methyl‐D‐aspartate (NMDA) receptors (NMDARs) and as such exhibit significant neuroprotective properties. These compounds also bind with a low affinity to binding sites whose pharmacological profiles are different from that of NMDARs. With the intention to develop new strategies of neuroprotection, we found it mandatory to investigate whether 1‐[1‐(2‐thienyl)cyclohexyl]piperidine (TCP) and gacyclidine… 
Synthesis of C5-tetrazole derivatives of 2-amino-adipic acid displaying NMDA glutamate receptor antagonism
C5 tetrazole-substituted of 2-amino-adipic acid represent an interesting series of new NMDA receptor antagonists and may be considered as a new strategy to develop ligands specifically targeted to synaptic or extra-synaptic NMDA receptors.
Effects of extracochlear gacyclidine perfusion on tinnitus in humans: a case series
Gacyclidine might present a potent drug for the suppression of sensorineural tinnitus in humans and therefore should be considered for future double-blinded, placebo-controlled clinical trials.
Current status of clinical trials for acute spinal cord injury.
Promising potential therapies for ASCI include riluzole, minocycline, erythropoietin, and the fusogen polyethylene glycol, as well as mild hypothermia, while trials of improved neuroprotective agents are required.
A Rat Brain Bicistronic Gene with an Internal Ribosome Entry Site Codes for a Phencyclidine-binding Protein with Cytotoxic Activity*
This rare mammalian bicistronic gene coded for two tightly interacting brain proteins forming a low affinity phencyclidine-binding entity in a synaptic membrane complex in rat brain synaptic membranes.
New perspectives for the treatment options in spinal cord injury
The goal of future treatment options for SCI is to find suitable new drugs or a combination of existing drugs and to use various cellular transplants, neurotrophic factors, myelin-inhibiting factors, tissue engineering and nano-drug delivery to improve both the functional and the pathological outcome in the inured patient.
Composition pharmaceutique et son application dans le domaine de la neurologie en tant qu'agent modulateur du systeme glutamatergique
Composition pharmaceutique et son application dans le domaine de la neurologie en tant qu'agent modulateur du systeme glutamatergiqueLa presente invention concerne une composition pharmaceutique


Characterization of ‘non‐N‐methyl‐d‐Aspartate’ binding sites for gacyclidine enantiomers in the rat cerebellar and telencephalic structures
This study demonstrates that the gacyclidine ‘non‐NMDA’ binding sites are associated with the dendritic trees of Purkinje cells, and shows that the radioligand binding to both cerebellar and telencephalic structures could be modulated by endogeneous factors which can be removed by a stringent prewashing procedure.
Differentiation of σ ligand‐activated receptor subtypes that modulate NMDA‐evoked [3H]‐noradrenaline release in rat hippocampal slices
1 It is now widely accepted that there are two classes of sigma (σ) binding sites, denoted σ1 and σ2, and recently σ3 subtype has been proposed. Selective σ1 and σ2 receptor agonists are known to
Gacyclidine: a new neuroprotective agent acting at the N-methyl-D-aspartate receptor.
It is concluded that gacyclidine exhibits neuroprotective effects similar to those of other NMDA receptor antagonists, with the advantage of being substantially less neurotoxic maybe due to its interaction with "non-NMDA" binding sites.
In vitro neuroprotection against glutamate toxicity provided by novel non‐competitive N‐methyl‐d‐aspartate antagonists
It is shown here that the (−) enantiomers have a significantly better protective effect than the (+)Enantiomers, but that the former are as efficient as the corresponding racemates.
Characterization of two novel σ receptor ligands: antidystonic effects in rats suggest σ receptor antagonism
The novel σ receptor ligands, N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine (BD1047) and 1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine (BD1063), were characterized in rats
The search for TCP analogues binding to the low affinity PCP receptor sites in the rat cerebellum
Abstract With the aim of obtaining selective ligands of the low affinity binding sites of [3H]-1-[1-(2-thienyl)cyclohexyl]piperidine ([3H]TCP) in the rat cerebellum, oxygen and sulfur atoms were
Interaction of gacyclidine enantiomers with ‘non-NMDA’ binding sites in the rat central nervous system
Preventing its interaction with NMDARs is demonstrated, through the use of its enantiomers, that gacyclidine also interacts with other ('non-NMDA') binding sites, which could exert a modulatory control on glutamatergic neurotransmission.
The low affinity PCP sites in the rat cerebellum not only bind TCP-like but also BTCP-like structures.
Congeners of the potent dopamine (DA) re-uptake inhibitor 1-[1-(2-benzo[b]thiophenyl)cyclohexyl]piperidine (BTCP) are unexpectedly able to bind in the rat cerebellum, although this structure is
Binding properties of [ 3 H ]gacyclidine (cis(pip/me)-1-[1-(2-thienyl)-2-methylcyclohexyl]piperidine) enantiomers in the rat central nervous system
Overall, this study showed that low affinity sites might constitute a heterogeneous population, which could include sigma receptors in the cerebellum, and has shown that these sites may be located in the molecular layer.
Characterization of two novel sigma receptor ligands: antidystonic effects in rats suggest sigma receptor antagonism.
BD1047 and BD1063 appear to act as antagonists at sigma sites and may represent promising new tools for probing other functional effects associated with sigma binding sites.