Pharmacology of cognition: a panacea for neuropsychiatric disease?

Bailey, Sarah; Neill, Joanna C.; Moran, Paula M.

doi:10.1111/bph.13956

Cited by 7 publications

(2 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MMN is not only a cognitive biomarker but also a biomarker for negative symptoms in schizophrenia [147]. The pharmacology of cognition as a panacea for neuropsychiatric diseases was recently published [148]. This is important because neuropsychological tests were unable to distinguish CIAS versus cognitive impairments after traumatic brain injury [149].…”

Section: Mismatch Negativitymentioning

confidence: 99%

Potential Role of Antipsychotic-Galantamine-Memantine Combination in the Treatment of Positive, Cognitive, and Negative Symptoms of Schizophrenia

Koola¹

2018

Complex Psychiatry

View full text Add to dashboard Cite

Schizophrenia is, in part, a cognitive illness. There are no approved medications for cognitive impairments associated with schizophrenia (CIAS) and primary negative symptoms. Cholinergic and glutamatergic systems, alpha-7 nicotinic acetylcholine (α-7nACh) and N-methyl-D-aspartate (NMDA) receptors, kynurenic acid (KYNA), and mismatch negativity have been implicated in the pathophysiology of CIAS and negative symptoms. Galantamine is an acetylcholinesterase inhibitor that is also a positive allosteric modulator at the α4β2 and α7nACh receptors. Memantine is a noncompetitive NMDA receptor antagonist. Galantamine and memantine alone and in combination were effective for cognition in animals and people with Alzheimer’s disease. The objective of this article is to critically dissect the published randomized controlled trials with galantamine and memantine for CIAS to highlight the efficacy signal. These studies may have failed to detect a clinically meaningful efficacy signal due to limitations, methodological issues, and possible medication nonadherence. There is evidence from a small open-label study that the galantamine-memantine combination may be effective for CIAS with kynurenine pathway metabolites as biomarkers to detect the severity of cognitive impairments. Given that there are no available treatments for cognitive impairments and primary negative symptoms in schizophrenia, testing of this “five-pronged strategy” (quintuple hypotheses: dopamine, nicotinic-cholinergic, glutamatergic/NMDA, GABA, and KYNA) is a “low-risk high-gain” approach that could be a major breakthrough in the field. The galantamine-memantine combination has the potential to treat positive, cognitive, and negative symptoms, and targeting the quintuple hypotheses concurrently may lead to a major scientific advancement – from antipsychotic treatment to antischizophrenia treatment.

show abstract

Section: Mismatch Negativitymentioning

confidence: 99%

Potential Role of Antipsychotic-Galantamine-Memantine Combination in the Treatment of Positive, Cognitive, and Negative Symptoms of Schizophrenia

Koola¹

2018

Complex Psychiatry

View full text Add to dashboard Cite

show abstract

“…Nicotinic and NMDA receptors seem to be the underlying mechanism of major symptoms and biomarkers in many neuropsychiatric diseases (Koola, 2018c; Koola et al, 2019) as shown in Figure 3. The pharmacology (same combinations) of cognition may be a solution in the treatment of neuropsychiatric disorders (Bailey, Neill, & Moran, 2017). The strategy of targeting nicotinic‐cholinergic and glutamatergic/NMDA systems simultaneously (Table 2) may be a golden opportunity for novel therapeutic discovery.…”

Section: Schizophrenia and Beyondmentioning

confidence: 99%

Alpha7 nicotinic‐N‐methyl‐D‐aspartate hypothesis in the treatment of schizophrenia and beyond

Koola

2020

Human Psychopharmacology

View full text Add to dashboard Cite

Development of novel treatments for positive, cognitive, and negative symptoms continue to be a high‐priority area of schizophrenia research and a major unmet clinical need. Given that all randomized controlled trials (RCTs) conducted to date failed with one add‐on medication/mechanism of action, future RCTs with the same approach are not warranted. Even if the field develops a medication for cognition, others are still needed to treat negative and positive symptoms. Therefore, fixing one domain does not completely solve the problem. Also, targeting the cholinergic system, glutamatergic system, and cholinergic plus alpha7 nicotinic and N‐methyl‐D‐aspartate (NMDA) receptors failed independently. Hence, targeting other less important pathophysiological mechanisms/targets is unlikely to be successful. Meta‐analyses of RCTs targeting major pathophysiological mechanisms have found some efficacy signal in schizophrenia; thus, combination treatments with different mechanisms of action may enhance the efficacy signal. The objective of this article is to highlight the importance of conducting RCTs with novel combination treatments in schizophrenia to develop antischizophrenia treatments. Positive RCTs with novel combination treatments that target the alpha7 nicotinic and NMDA receptors simultaneously may lead to a disease‐modifying therapeutic armamentarium in schizophrenia. Novel combination treatments that concurrently improve the three domains of psychopathology and several prognostic and theranostic biomarkers may facilitate therapeutic discovery in schizophrenia.

show abstract

Natural products-based polypharmacological modulation of the peripheral immune system for the treatment of neuropsychiatric disorders

Mok

Dias

et al. 2020

Pharmacology & Therapeutics

View full text Add to dashboard Cite

Pharmacology of cognition: a panacea for neuropsychiatric disease?

Abstract: Linked Articles This article is part of a themed section on Pharmacology of Cognition: a Panacea for Neuropsychiatric Disease? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.19/issuetoc

Cited by 7 publications

References 16 publications

Potential Role of Antipsychotic-Galantamine-Memantine Combination in the Treatment of Positive, Cognitive, and Negative Symptoms of Schizophrenia

Potential Role of Antipsychotic-Galantamine-Memantine Combination in the Treatment of Positive, Cognitive, and Negative Symptoms of Schizophrenia

Alpha7 nicotinic‐N‐methyl‐D‐aspartate hypothesis in the treatment of schizophrenia and beyond

Natural products-based polypharmacological modulation of the peripheral immune system for the treatment of neuropsychiatric disorders

Contact Info

Product

Resources

About