Galantamine added to antipsychotic treatment in chronic schizophrenia: Cognitive improvement?

Norén, Urban; Björner, A.; Sonesson, Ove; Eriksson, Lars

doi:10.1016/j.schres.2006.03.039

Cited by 15 publications

(10 citation statements)

References 8 publications

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“…An alkaloid originally isolated from snowdrop flowers, galantamine is currently used to treat mild-to-moderate AD (Corey-Bloom, 2003) and has recently also been tested as an adjuvant therapy to improve cognitive function in schizophrenia (Norén et al, 2006;Schubert et al, 2006). Although galantamine is also a weak reversible cholinesterase inhibitor, its nicotinic APL action seems to be an important determinant of its clinical effectiveness (reviewed in Corey-Bloom, 2003;Maelicke and Albuquerque, 1996;Pereira et al, 2002).…”

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confidence: 99%

Competitive Antagonism between the Nicotinic Allosteric Potentiating Ligand Galantamine and Kynurenic Acid at α7* Nicotinic Receptors

Lopes

Pereira²,

Wu³

et al. 2007

J Pharmacol Exp Ther

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Galantamine, a drug used to treat Alzheimer's disease, is a nicotinic allosteric potentiating ligand, and kynurenic acid (KYNA), a neuroactive metabolite of the kynurenine pathway, is an endogenous noncompetitive inhibitor of ␣7* nicotinic receptors (nAChRs) [the asterisk next to the nAChR subunit is intended to indicate that the exact subunit composition of the receptor is not known (Pharmacol Rev 51:397-401, 1999)]. Here, possible interactions between KYNA and galantamine at ␣7* nAChRs were examined in vitro and in vivo. In the presence of tetrodotoxin (TTX), approximately 85% of cultured hippocampal neurons responded to choline (0.3-30 mM) with ␣7* nAChR-subserved whole-cell (type IA) currents. In the absence of TTX and in the presence of glutamate receptor antagonists, choline triggered inhibitory postsynaptic currents (IPSCs) by activating ␣7* nAChRs on GABAergic neurons synapsing onto the neurons under study. Galantamine (1-10 M) potentiated, whereas KYNA (10 nM-1 mM) inhibited, choline-triggered responses. Galantamine (1 M), applied before KYNA, shifted to the right the concentration-response relationship for KYNA to inhibit type IA currents, increasing the IC 50 of KYNA from 13.9 Ϯ 8.3 to 271 Ϯ 131 M. Galantamine, applied before or after KYNA, antagonized inhibition of choline-triggered IPSCs by KYNA. Local infusion of KYNA (100 nM) in the rat striatum reduced extracellular dopamine levels in vivo. This effect resulted from ␣7* nAChR inhibition and was blocked by coapplied galantamine (1-5 M). It is concluded that galantamine competitively antagonizes the actions of KYNA on ␣7* nAChRs. Reducing ␣7* nAChR inhibition by endogenous KYNA may be an important determinant of the effectiveness of galantamine in neurological and psychiatric disorders associated with decreased ␣7* nAChR activity in the brain.

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confidence: 99%

Competitive Antagonism between the Nicotinic Allosteric Potentiating Ligand Galantamine and Kynurenic Acid at α7* Nicotinic Receptors

Lopes

Pereira²,

Wu³

et al. 2007

J Pharmacol Exp Ther

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“…The studies with galantamine have had mixed results. Of the five double-blind, placebo-controlled, multiweek trials, four have provided some evidence of improvements in cognitive function with galantamine compared to placebo Lee et al 2007b;Noren et al 2006;Schubert et al 2006). One of these was a relatively large-scale study (86 patients) that found greater improvements on galantamine versus placebo for Digit Symbol and California Verbal Learning Performance, though more improvement on placebo for a Continuous Performance Test measure ).…”

Section: Cholinesterase Inhibitorsmentioning

confidence: 99%

“…One of these was a relatively large-scale study (86 patients) that found greater improvements on galantamine versus placebo for Digit Symbol and California Verbal Learning Performance, though more improvement on placebo for a Continuous Performance Test measure ). However, one was a very small study (only 12 patients) which did not conduct formal statistical tests and provided only qualitative evidence for the benefits of galantamine (Noren et al 2006). The most recent double-blind study was of a shorter duration (8 weeks) than the majority of the previous studies (12 weeks), and found that instead of improving cognitive function, galantamine impaired Continuous Performance Test -Identical Pairs (CPT-IP) performance, Stroop Interference, and some aspects of working memory ).…”

Section: Cholinesterase Inhibitorsmentioning

confidence: 99%

Pharmacological Strategies for Enhancing Cognition in Schizophrenia

Deanna

2010

Behavioral Neurobiology of Schizophrenia and Its Treatment

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“…There is some evidence from animal studies that risperidone and galantamine act synergistically to increase dopamine activity in the PFC (Wang et al 2007). Early studies in small numbers of patients suggested that adjunctive galantamine may be of benefit in schizophrenia (Bora et al 2005;Noren et al 2006;Schubert et al 2006), although negative results were also reported Lee et al 2007). A larger study by Buchanan et al (2008) produced mixed results.…”

Section: Galantaminementioning

confidence: 99%