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1 Aminocyclopropanecarboxylic Acid

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Phil Skolnick – One of the best experts on this subject based on the ideXlab platform.

  • 1 Aminocyclopropanecarboxylic Acid acpc produces procognitive but not antipsychotic like effects in rats
    Psychopharmacology, 2015
    Co-Authors: Piotr Popik, Malgorzata Holuj, Agnieszka Nikiforuk, Tomasz Kos, Ramon Trullas, Phil Skolnick

    Abstract:

    Rationale
    In addition to the negative and positive symptoms of schizophrenia, cognitive deficits, including prefrontal cortical dysfunction, are now recognized as core features of this disorder. Compounds increasing the NMDA receptor function via the strychnine-insensitive glycine receptors have been proposed as potential antipsychotics. Depending on the ambient concentrations of glutamate and glycine, 1Aminocyclopropanecarboxylic Acid (ACPC) behaves as either a partial agonist or a functional antagonist at the strychnine-insensitive glycine receptors.

  • 1Aminocyclopropanecarboxylic Acid (ACPC) produces procognitive but not antipsychotic-like effects in rats
    Psychopharmacology, 2015
    Co-Authors: Piotr Popik, Malgorzata Holuj, Agnieszka Nikiforuk, Tomasz Kos, Ramon Trullas, Phil Skolnick

    Abstract:

    Rationale In addition to the negative and positive symptoms of schizophrenia, cognitive deficits, including prefrontal cortical dysfunction, are now recognized as core features of this disorder. Compounds increasing the NMDA receptor function via the strychnine-insensitive glycine receptors have been proposed as potential antipsychotics. Depending on the ambient concentrations of glutamate and glycine, 1Aminocyclopropanecarboxylic Acid (ACPC) behaves as either a partial agonist or a functional antagonist at the strychnine-insensitive glycine receptors. Objectives We investigated the procognitive and antipsychotic-like effects of ACPC in rats treated with phencyclidine (PCP) or ketamine (KET), compounds that produce psychotic-like symptoms in humans and laboratory animals. Methods Cognitive effects were investigated in the novel object recognition (NOR) and attentional set-shifting tests (ASST). In addition, the effects of ACPC were investigated in PCP-induced hyperactivity, conditioned avoidance response (CAR), and prepulse inhibition (PPI) tests. The effects on attention and impulsivity were measured in the five-choice serial reaction time task (5-CSRTT). Results ACPC (200–400 mg/kg) inhibited memory fading in naive rats and like clozapine prevented PCP- and KET-induced amnesia in the NOR. In naive animals, ACPC at 400 but not 200 mg/kg enhanced cognitive flexibility in the ASST, as the animals required fewer trials to reach the criteria during the extra-dimensional phase. In contrast, ACPC did not affect PCP-induced hyperactivity, CAR, and PPI as well as attention and impulsivity in the 5-CSRTT. Conclusion The present study demonstrates that ACPC enhanced both object recognition memory and cognitive flexibility dependent on the prefrontal cortex, but did not affect impulsivity nor exhibit an antipsychotic-like profile.

  • putative partial agonist 1 Aminocyclopropanecarboxylic Acid acts concurrently as a glycine site agonist and a glutamate site antagonist at n methyl d aspartate receptors
    Molecular Pharmacology, 1999
    Co-Authors: Rinat Nahumlevy, Phil Skolnick, Linda H Fossom, Morris Benveniste

    Abstract:

    1Aminocyclopropanecarboxylic Acid (ACPC) has been shown to protect against neuronal cell death after ischemic insult in vivo. Such results can be correlated with in vitro assays in which ACPC protected neurons against glutamate-induced neurotoxicity by reducing the activity of N -methyl-d-aspartate (NMDA) channel activation. Electrophysiological studies have determined that ACPC inhibits NMDA receptor activity by acting as a glycine-binding site partial agonist. In this study, rapid drug perfusion combined with whole-cell voltage-clamp was used to elicit and measure the effects of ACPC on NMDA receptor-mediated responses from cultured hippocampal neurons and cerebellar granule cells. The ACPC steady-state dose-response curve had both stimulatory and inhibitory phases. Half-maximal activation by ACPC as a glycine-site agonist was 0.7 to 0.9 μM. Half-maximal inhibition by ACPC was dependent on NMDA concentration. Peak responses to a >100 μM ACPC pulse in the presence of 1 μM glutamate were similar to those of glycine but decayed to a steady-state amplitude below that of glycine. The removal of ACPC initially caused an increase in inward current followed by a subsequent decrease to baseline levels. This suggests that relief of low-affinity antagonism occurs before high-affinity agonist dissociation. Simulations of ACPC action by a two glutamate-binding site/two glycine-binding site model for NMDA channel activation in conjunction with the concurrent role of ACPC as a glycine-site full agonist and glutamate-site competitive antagonist were able to successfully approximate experimental results.

Ramon Trullas – One of the best experts on this subject based on the ideXlab platform.

  • 1Aminocyclopropanecarboxylic Acid (ACPC) produces procognitive but not antipsychotic-like effects in rats
    Psychopharmacology, 2015
    Co-Authors: Piotr Popik, Malgorzata Holuj, Agnieszka Nikiforuk, Tomasz Kos, Ramon Trullas, Phil Skolnick

    Abstract:

    Rationale In addition to the negative and positive symptoms of schizophrenia, cognitive deficits, including prefrontal cortical dysfunction, are now recognized as core features of this disorder. Compounds increasing the NMDA receptor function via the strychnine-insensitive glycine receptors have been proposed as potential antipsychotics. Depending on the ambient concentrations of glutamate and glycine, 1Aminocyclopropanecarboxylic Acid (ACPC) behaves as either a partial agonist or a functional antagonist at the strychnine-insensitive glycine receptors. Objectives We investigated the procognitive and antipsychotic-like effects of ACPC in rats treated with phencyclidine (PCP) or ketamine (KET), compounds that produce psychotic-like symptoms in humans and laboratory animals. Methods Cognitive effects were investigated in the novel object recognition (NOR) and attentional set-shifting tests (ASST). In addition, the effects of ACPC were investigated in PCP-induced hyperactivity, conditioned avoidance response (CAR), and prepulse inhibition (PPI) tests. The effects on attention and impulsivity were measured in the five-choice serial reaction time task (5-CSRTT). Results ACPC (200–400 mg/kg) inhibited memory fading in naive rats and like clozapine prevented PCP- and KET-induced amnesia in the NOR. In naive animals, ACPC at 400 but not 200 mg/kg enhanced cognitive flexibility in the ASST, as the animals required fewer trials to reach the criteria during the extra-dimensional phase. In contrast, ACPC did not affect PCP-induced hyperactivity, CAR, and PPI as well as attention and impulsivity in the 5-CSRTT. Conclusion The present study demonstrates that ACPC enhanced both object recognition memory and cognitive flexibility dependent on the prefrontal cortex, but did not affect impulsivity nor exhibit an antipsychotic-like profile.

  • 1 Aminocyclopropanecarboxylic Acid acpc produces procognitive but not antipsychotic like effects in rats
    Psychopharmacology, 2015
    Co-Authors: Piotr Popik, Malgorzata Holuj, Agnieszka Nikiforuk, Tomasz Kos, Ramon Trullas, Phil Skolnick

    Abstract:

    Rationale
    In addition to the negative and positive symptoms of schizophrenia, cognitive deficits, including prefrontal cortical dysfunction, are now recognized as core features of this disorder. Compounds increasing the NMDA receptor function via the strychnine-insensitive glycine receptors have been proposed as potential antipsychotics. Depending on the ambient concentrations of glutamate and glycine, 1Aminocyclopropanecarboxylic Acid (ACPC) behaves as either a partial agonist or a functional antagonist at the strychnine-insensitive glycine receptors.

  • effect of 1 Aminocyclopropanecarboxylic Acid on n methyl d aspartate stimulated 3h noradrenaline release in rat hippocampal synaptosomes
    British Journal of Pharmacology, 1996
    Co-Authors: M V Clos, Ramon Trullas, Garcia A Sanz, Albert Badia

    Abstract:

    1. The effect of 1Aminocyclopropanecarboxylic Acid (ACPC), a partial agonist at the glycine site of the N-methyl-D-aspartate (NMDA) receptor complex that exhibits neuroprotective, anxiolytic and antidepressant-like actions, was investigated in a functional assay for presynaptic NMDA receptors. 2. NMDA (100 microM) produced a 36% increase of tritium efflux above basal efflux in rat hippocampal synaptosomes preincubated with [3H]-noradrenaline ([3H]-NA), reflecting a release of tritiated noradrenaline. This effect was prevented by 10 microM 7-chlorokynurenic Acid, an antagonist of the glycine site of the NMDA receptor. 3. Glycine enhanced the effect of NMDA with Emax and EC50 values of 84 +/- 11% and 1.82 +/- 0.04 microM, respectively. ACPC potentiated the effect of NMDA on tritium overflow with a lower EC50 (43 +/- 6 nM) and a lower maximal effect (Emax = 40 +/- 9%) than glycine. Furthermore, ACPC (0.1 microM) shifted the EC50 of glycine from 1.82 microM to > or = 3 mM. 4. These results show that ACPC can reduce the potentiation by glycine of NMDA-evoked [3H]-NA release and hence, may act as an antagonist at the glycine site of presynaptic hippocampal NMDA receptors when the concentration of glycine is high.

Piotr Popik – One of the best experts on this subject based on the ideXlab platform.

  • 1 Aminocyclopropanecarboxylic Acid acpc produces procognitive but not antipsychotic like effects in rats
    Psychopharmacology, 2015
    Co-Authors: Piotr Popik, Malgorzata Holuj, Agnieszka Nikiforuk, Tomasz Kos, Ramon Trullas, Phil Skolnick

    Abstract:

    Rationale
    In addition to the negative and positive symptoms of schizophrenia, cognitive deficits, including prefrontal cortical dysfunction, are now recognized as core features of this disorder. Compounds increasing the NMDA receptor function via the strychnine-insensitive glycine receptors have been proposed as potential antipsychotics. Depending on the ambient concentrations of glutamate and glycine, 1Aminocyclopropanecarboxylic Acid (ACPC) behaves as either a partial agonist or a functional antagonist at the strychnine-insensitive glycine receptors.

  • 1Aminocyclopropanecarboxylic Acid (ACPC) produces procognitive but not antipsychotic-like effects in rats
    Psychopharmacology, 2015
    Co-Authors: Piotr Popik, Malgorzata Holuj, Agnieszka Nikiforuk, Tomasz Kos, Ramon Trullas, Phil Skolnick

    Abstract:

    Rationale In addition to the negative and positive symptoms of schizophrenia, cognitive deficits, including prefrontal cortical dysfunction, are now recognized as core features of this disorder. Compounds increasing the NMDA receptor function via the strychnine-insensitive glycine receptors have been proposed as potential antipsychotics. Depending on the ambient concentrations of glutamate and glycine, 1Aminocyclopropanecarboxylic Acid (ACPC) behaves as either a partial agonist or a functional antagonist at the strychnine-insensitive glycine receptors. Objectives We investigated the procognitive and antipsychotic-like effects of ACPC in rats treated with phencyclidine (PCP) or ketamine (KET), compounds that produce psychotic-like symptoms in humans and laboratory animals. Methods Cognitive effects were investigated in the novel object recognition (NOR) and attentional set-shifting tests (ASST). In addition, the effects of ACPC were investigated in PCP-induced hyperactivity, conditioned avoidance response (CAR), and prepulse inhibition (PPI) tests. The effects on attention and impulsivity were measured in the five-choice serial reaction time task (5-CSRTT). Results ACPC (200–400 mg/kg) inhibited memory fading in naive rats and like clozapine prevented PCP- and KET-induced amnesia in the NOR. In naive animals, ACPC at 400 but not 200 mg/kg enhanced cognitive flexibility in the ASST, as the animals required fewer trials to reach the criteria during the extra-dimensional phase. In contrast, ACPC did not affect PCP-induced hyperactivity, CAR, and PPI as well as attention and impulsivity in the 5-CSRTT. Conclusion The present study demonstrates that ACPC enhanced both object recognition memory and cognitive flexibility dependent on the prefrontal cortex, but did not affect impulsivity nor exhibit an antipsychotic-like profile.

  • 3h 1 Aminocyclopropanecarboxylic Acid a novel probe for strychnine insensitive glycine receptors
    European Journal of Pharmacology, 1995
    Co-Authors: Piotr Popik, Gabriel Nowak, Anita H Lewin, Richard T Layer, Berthold Berrang, Phil Skolnick

    Abstract:

    Abstract [3H]1Aminocyclopropanecarboxylic Acid (ACPC) exhibits high affinity, specific binding to strychnine-insensitive glycine receptors. In extensively washed rat forebrain membranes, the specific binding of [3H]ACPC was optimal at 25°C in the presence of 10 mM MgCl2. Comparable levels of specific [3H]ACPC binding were obtained using centrifugation and filtration for separation of bound from free radioligand. [3H]ACPC labels two sites with Kd1 and Bmax1 values of 129±34 nM and 2.30±0.37 pmol/mg protein and Kd2 and Bmax2 values of 7.26±1.69 μM and 20.6±2.2 pmol/mg protein for the high and low affinity sites, respectively. The Kd of [3H]ACPC (66 nM) estimated under non-equilibrium conditions (koff=8.91±0.78×10−3 s−1; kon=1.35×10−4 nM−1 s−1) was similar to the value obtained for the high affinity site obtained by equilibrium binding. The Kd1 of [3H]ACPC is in good agreement with the previously reported Ki values of ACPC to inhibit the binding of other glycinergic ligands including [3H]glycine, [3H]5,7-dichlorokynurenic Acid (5,7-DCKA) and [3H]L-689,560 ((±)-4-(trans)-2-carboxy-5,7-dichloro-4-phenylaminocarbonylamino-1,2,3,4-tetrahydroquinoline). Moreover, the potencies of a series of glycine site ligands, including glycine, ACPC, 1-aminocyclobutanecarboxylic Acid (ACBC), 5,7-DCKA, 7-chlorokynurenic Acid (7-CKA), R(+)-3-amino-1-hydroxy-2-pyrrolidine (HA-966) and D -serine, to inhibit [3H]ACPC binding were highly correlated with their potencies to inhibit [3H]glycine and [3H]5,7-DCKA binding (r2=0.98−0.51). These results demonstrate that [3H]ACPC is a useful tool for examining the neurochemical and pharmacological properties of strychnine-insensitive glycine receptors.