Evaluation of the phencyclidine-like discriminative stimulus effects of novel NMDA channel blockers in rats

Nicholson, Katherine L.; Balster, Robert L.

doi:10.1007/s00213-003-1527-6

Cited by 15 publications

(6 citation statements)

References 54 publications

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“…Excessiveo rabnormalNMDA receptoractivity hasbeen linked withn umerous neuropathologicalconditionsincluding acuten eurotoxicity whicho ccurs subsequenttoheadtraumaand ischemicstroke aswell asa numberof chronic, neurodegenerativedisorders including neuropathicpain [26].…”

Section: Discussionmentioning

confidence: 99%

Synthesis and analgesic effects of 1-[1-(2-methylphenyl)(cyclohexyl)]-3-piperidinol as a new derivative of phencyclidine in mice

Ahmadi

Solati

Hajikhani

et al. 2011

Arzneimittelforschung

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Phencyclidine (1-(1-phenylcyclohexyl) piperidine, CAS 956-90-1, PCP, I) and its derivatives have shown many analgesic effects. In this research, a new derivative of PCP (1-[1-(2-methylphenyl) (cyclohexyl)l3-piperidinol, PD, II) was synthesized and its analgesic (acute and chronic pains) effects were examined on rats using tail immersion (as a model of acute thermal pain) and formalin (as a model of acute and chronic chemical pain) tests and the results are compared to PCP and control groups. The results indicated that II produces higher analgesic effects in the tail immersion test compared to the PCP and control groups, with a marked and significant increase in tail immersion latency for the doses 1, 5 and 10 mg/kg. The formalin test showed that PD (II) is not effective in acute chemical pain (phase I, 0-5 min after injection) in all doses but chronic pain (initial-phase II, 15-40 min after injection) is significantly attenuated by this compound compared to PCP and saline (control) in dosesof 5 and 10 mg/kg. It is concluded that II is effective in acute thermal (in all doses) and chronic (doses of 5 and 10 mg/kg) pains; however, it is not effective in acute chemical pain compared to PCP and control.

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Section: Discussionmentioning

confidence: 99%

Synthesis and analgesic effects of 1-[1-(2-methylphenyl)(cyclohexyl)]-3-piperidinol as a new derivative of phencyclidine in mice

Ahmadi

Solati

Hajikhani

et al. 2011

Arzneimittelforschung

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“…GLYX-13 did not show any ketamine-like discriminative stimulus effects (Figure 3E) or sedative effects (Figure 3F) in rats trained to discriminate 10 mg/kg ketamine from saline. Using this drug discrimination protocol, NMDAR antagonists that have been shown to have psychotomimetic properties show ketamine-like discriminative stimulus effects, while NMDAR glycine site modulators do not show ketamine/PCP discriminative stimulus effects or psychotomimetic effects in humans [58,59]. In addition, GLYX-13 (10 mg/kg IV) did not produce a rewarding effect in the conditioned place-preference test (Figure 3G), relevant to the addictive side effects of NMDAR anatagonists such as ketamine or PCP [60], and did not suppress pre-pulse inhibition (Figure 3H) relevant to the sensory-motor gating deficits seen following ketamine or PCP that are associated with the positive symptoms of schizophrenia [61].…”

Section: Pharmacologymentioning

confidence: 99%

GLYX-13, an NMDA receptor glycine site functional partial agonist enhances cognition and produces antidepressant effects without the psychotomimetic side effects of NMDA receptor antagonists

Moskal¹,

Burch²,

Burgdorf³

et al. 2013

Expert Opinion on Investigational Drugs

116

112

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Introduction The N-methyl-d-aspartate receptor-ionophore complex plays a key role in learning and memory and has efficacy in animals and humans with affective disorders. GLYX-13 is an N-methyl-d-aspartate receptor (NMDAR) glycine-site functional partial agonist and cognitive enhancer that also shows rapid antidepressant activity without psychotomimetic side effects. Areas covered The authors review the mechanism of action of GLYX-13 that was investigated in preclinical studies and evaluated in clinical studies. Specifically, the authors review its pharmacology, pharmacokinetics, and drug safety that were demonstrated in clinical studies. Expert opinion NMDAR full antagonists can produce rapid antidepressant effects in treatment-resistant subjects; however, they are often accompanied by psychotomimetic effects that make chronic use outside of a clinical trial inpatient setting problematic. GLYX-13 appears to exert its antidepressant effects in the frontal cortex via NMDAR-triggered synaptic plasticity. Understanding the mechanistic underpinning of GLYX-13’s antidepressant action should provide both novel insights into the role of the glutamatergic system in depression and identify new targets for therapeutic development.

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“…Some of them were described as effective antagonists of the phencyclidine (PCP) site (Rogawski et al 1989). However, most tetrahydroisoquinolines do not substitute for PCP (Nicholson and Balster 2003). …”

Section: Introductionmentioning

confidence: 99%

1-Methyl-1,2,3,4-Tetrahydroisoquinoline, an Endogenous Amine with Unexpected Mechanism of Action: New Vistas of Therapeutic Application

2013

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This review outlines the effects of 1,2,3,4-tetrahydroisoquinoline (TIQ) and its derivative, 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ), endogenous substances imbued with high pharmacological potential and broad spectrum of action in brain. 1MeTIQ has gained special interest as a neuroprotectant, and its ability to antagonize the behavioral syndrome produced by well-known neurotoxins (e.g., MPTP; rotenone). This review is thus focused on mechanisms of action of 1MeTIQ in behavioral, neurochemical, and molecular studies in rodents; also, effects of TIQ and 1MeTIQ on dopamine metabolism; and neuroprotective properties of TIQ and 1MeTIQ in vitro and in vivo. Finally, antiaddictive properties of 1MeTIQ will be described in cocaine self-administered rats. Findings implicate TIQ and especially its methyl derivative 1MeTIQ in unique and complex mechanisms of neuroprotection in various neurodegenerative illnesses of the central nervous system. We believe that MAO inhibition, free radicals scavenging properties, and antagonism to the glutamatergic system may play an essential role in neuroprotection. In addition, the results strongly support the view that 1MeTIQ has a considerable potential as a drug for combating substance abuse, through the attenuation of craving.

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Evaluation of the phencyclidine-like discriminative stimulus effects of novel NMDA channel blockers in rats

Cited by 15 publications

References 54 publications

Synthesis and analgesic effects of 1-[1-(2-methylphenyl)(cyclohexyl)]-3-piperidinol as a new derivative of phencyclidine in mice

Synthesis and analgesic effects of 1-[1-(2-methylphenyl)(cyclohexyl)]-3-piperidinol as a new derivative of phencyclidine in mice

GLYX-13, an NMDA receptor glycine site functional partial agonist enhances cognition and produces antidepressant effects without the psychotomimetic side effects of NMDA receptor antagonists

1-Methyl-1,2,3,4-Tetrahydroisoquinoline, an Endogenous Amine with Unexpected Mechanism of Action: New Vistas of Therapeutic Application

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