The use of cholecystokinin in schizophrenia: a review

Montgomery, Stuart; Green, Mary C. D.

doi:10.1017/s0033291700008278

Cited by 42 publications

(14 citation statements)

References 44 publications

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“…Third, in terms of GABA receptor allosteric modulators, selective GABA A agonists and GABA B antagonists and allosteric modulators at GABA A receptor subtypes (α1, 2, 3 and 5) are also promising therapeutic agents for schizophrenia [25]; Fourth, in terms of neuropeptides, cholecystokinin (CCK) receptor agonists, cannabinoid 1 (CB1) receptor antagonists and neurokinin 3 (NK3) receptor antagonists have been proposed as the potential antipsychotic strategies [42,43,44]; Fifth, since PDE contributes to degradation of the intracellular signaling pathways including cyclic AMP and cyclic GMP which have been associated with functions of dopamine and other neurotransmitters, PDE inhibitors have been proposed as potential therapeutic strategies for treating positive, negative and cognitive symptoms [37]; Sixth, since the relationship between elevated levels of kynurenic acid and declines in cognitive function in schizophrenia have been presented, KAT II inhibitors have been proposed as another strategy to treating cognitive symptoms [38]; Seventh, because of a possible relationship between inflammation and schizophrenia, anti-inflammatory agents have been evaluated in treating the early stage of schizophrenia [45,46]; Lastly, anti-oxidants have been evaluated for their ability to enhance neuroprotection and as an adjunctive strategy. …”

Section: Unmet Needs In the Current Antipsychotic Medications For mentioning

confidence: 99%

A Novel Bio-Psychosocial-Behavioral Treatment Model in Schizophrenia

Kim

Choi

Park

2017

IJMS

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Despite the substantial burden of illness in schizophrenia, there has been a discrepancy between the beneficial effects of an increased use of antipsychotic medications and achieving limited recovery or remission. Because the focus of the most common antipsychotic medications is on dopamine, which is associated with positive symptoms, there is an unmet need for patients with negative symptoms. Since cognitive and negative symptoms rather than positive symptoms are more closely associated with psychosocial impairments in patients with schizophrenia, the non-dopaminergic systems including glutamate and γ-aminobutyric acid (GABA) of the prefrontal cortex should be of concern as well. The balance of excitation and inhibition has been associated with epigenetic modifications and thus can be analyzed in terms of a neurodevelopmental and neural circuitry perspective. Hence, a novel bio-psychosocial-behavioral model for the treatment of schizophrenia is needed to account for the non-dopaminergic systems involved in schizophrenia, rather than dopaminergic mechanisms. This model can be understood from the viewpoint of neurodevelopment and neural circuitry and should include the staging care, personalized care, preventive care, reducing the cognitive deficits, and reducing stigma. Thomas R. Insel proposed this as a goal for schizophrenia treatment to be achieved by 2030.

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Section: Unmet Needs In the Current Antipsychotic Medications For mentioning

confidence: 99%

A Novel Bio-Psychosocial-Behavioral Treatment Model in Schizophrenia

Kim

Choi

Park

2017

IJMS

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“…Most research on the potential antipsychotic effects of CCK has used CCK or CCK analogues that nonselectively activate both CCK-A and CCK-B receptors. In this regard, early clinical trials using nonspecific CCK agonists and its analogues to treat schizophrenia patients did not support a role for CCK as an antipsychotic drug (Montgomery and Green 1988). However, the development of specific CCK-A and CCK-B agonists has made it possible to differentiate the pharmacological effects of CCK at each CCK receptor.…”

Section: Introductionmentioning

confidence: 99%

SR146131, a cholecystokinin-A receptor agonist, antagonizes prepulse inhibition deficits produced by dizocilpine and DOI

Feifel

2002

Psychopharmacology

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The lack of an effect of SR146131 on amphetamine-induced disruption of PPI suggests that a selective nonpeptide CCK-A agonist may not produce antipsychotic-like effects on dopamine transmission. However, the unexpected effects of SR146131 on dizocilpine and DOI-induced PPI deficits are consistent with the effects of drugs that inhibit transmission in the 5HT2A receptor system, including atypical antipsychotic drugs. Possible mechanisms underlying these findings are discussed.

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“…Cholecystokinin (CCK) agonists were among the earliest to be evaluated but results have been equivocal (Montgomery and Green, 1988). Because of the implication of cannabinoid (CB) mechanisms in schizophrenia (Müller-Vahl et al, 2008), the cannabinoid receptor subfamily has received considerable attention as a potential antipsychotic target with CB1 antagonists being of greatest interest.…”

Section: Novel Therapeutic Targets and Emerging Treatment Strategiesmentioning

confidence: 99%

New drug developments in psychosis: Challenges, opportunities and strategies

Keshavan

Lawler

Nasrallah

et al. 2017

Progress in Neurobiology

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All currently approved drugs for schizophrenia work mainly by dopaminergic antagonism. While they are efficacious for psychotic symptoms, their efficacy is limited for negative symptoms and cognitive deficits which underlie the substantive disability in this illness. Recent insights into the biological basis of schizophrenia, especially in relation to non-dopaminergic mechanisms, have raised the efforts to find novel and effective drug targets, though with relatively little success thus far. Potential impediments to novel drug discovery include the continued use of symptom based disease definitions which leads to etiological and pathophysiological heterogeneity, lack of valid preclinical models for drug testing, and design limitations in clinical trials. These roadblocks can be addressed by (i) characterizing trans-diagnostic, translational pathophysiological dimensions as potential treatment targets, (ii) efficiency, accountability and , transparency in approaches to the clinical trials process, and (iii) leveraging recent advances in genetics and in vitro phenotypes. Accomplishing these goals is urgent given the significant unmet needs in the pharmacological treatment of schizophrenia. As this happens, it is imperative that clinicians employ optimal dosing, measurement-based care, and other best practices in utilizing existing treatments to optimize outcomes for their patients today.

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The use of cholecystokinin in schizophrenia: a review

Cited by 42 publications

References 44 publications

A Novel Bio-Psychosocial-Behavioral Treatment Model in Schizophrenia

A Novel Bio-Psychosocial-Behavioral Treatment Model in Schizophrenia

SR146131, a cholecystokinin-A receptor agonist, antagonizes prepulse inhibition deficits produced by dizocilpine and DOI

New drug developments in psychosis: Challenges, opportunities and strategies

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