Effects of adjunct galantamine to risperidone, or haloperidol, in animal models of antipsychotic activity and extrapyramidal side-effect liability: involvement of the cholinergic muscarinic receptor

Wadenberg, Marie-Louise G.; Fjällström, Ann-Kristin; Federley, Malin; Persson, Pernilla; Stenqvist, Pia

doi:10.1017/s1461145710000921

Cited by 10 publications

(4 citation statements)

References 49 publications

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“…We have found that galantamine improves apomorphine-and isolation rearing-induced PPI deficits via an activation of the muscarinic receptors, especially M 1 (34,75). In addition, Wadenberg et al (66) recently reported that pretreatment with scopolamine, but not mecamylamine, completely reversed the enhancing effects of galantamine, when co-administered with haloperidol, in the conditioned avoidance response test. Although the inhibitory effect of galantamine on acetylcholinesterase is weak, microdialysis studies show that systemic administration of galantamine increases the extracellular ACh levels in mice (34) and rats (30).…”

Section: Schizophreniamentioning

confidence: 61%

“…Wiker et al (65) reported that galantamine at doses of 5 mg/kg alone attenuated the conditioned avoidance response, and at lower doses (1 mg/kg) it potentiated typical antipsychotic racloprideinduced avoidance response in rats. In addition, adjunctive galantamine (1.25 mg/kg) also enhanced the antipsychotic-like effects of haloperidol and risperidone in the conditioned avoidance response test (66).…”

Section: Schizophreniamentioning

confidence: 94%

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Pharmacological Aspects of the Acetylcholinesterase Inhibitor Galantamine

et al. 2011

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Abstract. Several lines of evidence suggest that cholinergic deficits may contribute to the pathophysiology of psychiatric disorders as well as Alzheimer's disease. There is growing clinical evidence that galantamine, currently used for the treatment of Alzheimer's disease, may improve cognitive dysfunction and psychiatric illness in schizophrenia, major depression, bipolar disorder, and alcohol abuse. Since galantamine is a rather weak acetylcholinesterase inhibitor, but has additional allosteric potentiating effects at nicotinic receptors, it affects not only cholinergic transmission but also other neurotransmitter systems such as monoamines, glutamate, and γ-aminobutyric acid (GABA) through its allosteric mechanism. It is likely that these effects may result in more beneficial effects. To understand the underlying mechanism for the clinical effectiveness of galantamine, neuropharmacological studies have been performed in animal models of several psychiatric disorders. These studies suggest that not only the nicotinic receptor-modulating properties but also the muscarinic receptor activation contribute to the antipsychotic effect and improvement of cognitive dysfunction by galantamine. This review summaries the current status on the pharmacology of galantamine, focusing on its effect on neurotransmitter release and pharmacological studies in animal models of psychiatric disorders.

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Section: Schizophreniamentioning

confidence: 61%

Section: Schizophreniamentioning

confidence: 94%

Pharmacological Aspects of the Acetylcholinesterase Inhibitor Galantamine

et al. 2011

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“…The followup study, however, demonstrated that any contribution to antipsychotic activity through galantamine is primarily mediated via muscarinic, but not nicotinic, acetylcholine receptors (Wadenberg et al, 2011). Nevertheless, α7-nAChRs might also participate in antipsychotic activity because the α7-nAChR agonist WYE-103914/SEN34625 potentiated the efficacy profile of risperidone in the CAR test (Marquis et al, 2011).…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 96%

Positive allosteric modulators of alpha 7 nicotinic acetylcholine receptors reverse ketamine-induced schizophrenia-like deficits in rats

et al. 2016

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“…Interestingly, galantamine has been reported to act partly on muscarinic receptor subtypes in some situations (Almasieh et al ). Indeed, Wadenberg et al () have shown that the potentiation by galantamine of antipsychotic drug efficacy in conditioned avoidance testing is prevented by muscarinic but not nicotinic receptor blockers, leading to their proposal that anti‐psychotic activity of galantamine involves mainly muscarinic receptors. This would be supported by evidence that the abnormal pre‐pulse inhibition seen in mice reared in isolation is normalised by a muscarinic action of galantamine (Yano et al ) and is not affected by a different acetylcholinesterase inhibitor such as donepezil (Koda et al ).…”

Section: Galantamine As a Pharmacological Toolmentioning

confidence: 99%

Does kynurenic acid act on nicotinic receptors? An assessment of the evidence

Stone

2019

Journal of Neurochemistry

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As a major metabolite of kynurenine in the oxidative metabolism of tryptophan, kynurenic acid is of considerable biological and clinical importance as an endogenous antagonist of glutamate in the central nervous system. It is most active as an antagonist at receptors sensitive to N‐methyl‐D‐aspartate (NMDA) which regulate neuronal excitability and plasticity, brain development and behaviour. It is also thought to play a causative role in hypo‐glutamatergic conditions such as schizophrenia, and a protective role in several neurodegenerative disorders, notably Huntington’s disease. An additional hypothesis, that kynurenic acid could block nicotinic receptors for acetylcholine in the central nervous system has been proposed as an alternative mechanism of action of kynurenate. However, the evidence for this alternative mechanism is highly controversial, partly because at least eight earlier studies concluded that kynurenic acid blocked NMDA receptors but not nicotinic receptors and five subsequent, independent studies designed to repeat the results have failed to do so. Many studies considered to support the alternative ‘nicotinic’ hypothesis have been based on the use of analogs of kynurenate such as 7‐chloro‐kynurenic acid, or putatively nicotinic modulators such as galantamine, but a detailed analysis of the pharmacology of these compounds suggests that the results have often been misinterpreted, especially since the pharmacology of galantamine itself has been disputed. This review examines the evidence in detail, with the conclusion that there is no confirmed, reliable evidence for an antagonist activity of kynurenic acid at nicotinic receptors. Therefore, since there is overwhelming evidence for kynurenate acting at ionotropic glutamate receptors, especially NMDAR glutamate and glycine sites, with some activity at GPR35 sites and Aryl Hydrocarbon Receptors, results with kynurenic acid should be interpreted only in terms of these confirmed sites of action.

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Effects of adjunct galantamine to risperidone, or haloperidol, in animal models of antipsychotic activity and extrapyramidal side-effect liability: involvement of the cholinergic muscarinic receptor

Cited by 10 publications

References 49 publications

Pharmacological Aspects of the Acetylcholinesterase Inhibitor Galantamine

Pharmacological Aspects of the Acetylcholinesterase Inhibitor Galantamine

Positive allosteric modulators of alpha 7 nicotinic acetylcholine receptors reverse ketamine-induced schizophrenia-like deficits in rats

Does kynurenic acid act on nicotinic receptors? An assessment of the evidence

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