Donepezil for negative signs in elderly patients with schizophrenia: an add-on, double-blind, crossover, placebo-controlled study

Mazeh, Doron; Zemishlani, Hanna; Barak, Yoram; Mirecki, Ilona; Paleacu, Diana

doi:10.1017/s1041610205003017

Cited by 28 publications

(17 citation statements)

References 13 publications

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“…However, a small randomized, double-blind trial showed positive outcomes when galantamine was administered as an add-on therapy to antipsychotics (Schubert et al, 2006). To date, no positive outcomes have been observed with donepezil or rivastigmine (Mazeh et al, 2006;Sharma et al, 2006). In light of the present results, we conclude that the antagonism of KYNAinduced inhibition of ␣7* nAChRs may be causally related to the effectiveness of galantamine in schizophrenia and AD.…”

Section: Discussionmentioning

confidence: 45%

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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Section: Discussionmentioning

confidence: 45%

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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“…Twenty-four double-blind studies were found (table II): 5 with rivastigmine, [37,39,41,46,50] 13 with donepezil [31,[33][34][35][36]38,40,[43][44][45][47][48]52] and 6 with galantamine. [32,42,49,51,53,54] Fifteen of these studies did not show an improvement in cognition in schizophrenia, [31,[33][34][35][36][37][39][40][45][46]48,50,[52][53][54] six found cognitive improvement [32,[41][42][43]49,51] and three [38,44,47] found improvement in psychopathology.…”

Section: Qualitative Review Of the Literaturementioning

confidence: 99%

“…[32,42,49,51,53,54] Fifteen of these studies did not show an improvement in cognition in schizophrenia, [31,[33][34][35][36][37][39][40][45][46]48,50,[52][53][54] six found cognitive improvement [32,[41][42][43]49,51] and three [38,44,47] found improvement in psychopathology.…”

Section: Qualitative Review Of the Literaturementioning

confidence: 99%

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Cholinesterase Inhibitors as Adjunctive Therapy in Patients with Schizophrenia and Schizoaffective Disorder

et al. 2010

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“…These studies were all done using donepezil as a neuroleptic augmentation treatment. Some (Mazeh et al, 2006;Stryjer et al, 2003) were in elderly patients or patients with known comorbid dementia. Others were in a general population of stable schizophrenic patients (Friedman et al, 2002;Stryjer et al, 2004;Tugal et al, 2004).…”

Section: Despite Clear Effects Of Other Cholinergic Compounds Chomentioning

confidence: 99%

Cholinergic Circuits and Signaling in the Pathophysiology of Schizophrenia

Berman

Talmage

Role

2007

International Review of Neurobiology

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Central cholinergic signaling has long been associated with aspects of memory, motivation, and mood, each affected functions in neuropsychiatric disorders such as schizophrenia. In this chapter, we review evidence related to the core hypothesis that dysregulation of central cholinergic signaling contributes to the pathophysiology of schizophrenia. Although central cholinergic circuits are resistant to simplification-particularly when one tries to parse the contributions of various classes of cholinergic receptors to disease related phenomena-the potential role of ACh signaling in Schizophrenia pathophysiology deserves careful consideration for prospective therapeutics. The established role of cholinergic circuits in attentional tuning is considered along with recent work on how the patterning of cholinergic activity may modulate corticostriatal circuits affected in schizophrenia.

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Donepezil for negative signs in elderly patients with schizophrenia: an add-on, double-blind, crossover, placebo-controlled study

Abstract: Donepezil does not seem to improve negative signs and cognitive impairment in elderly patients with chronic schizophrenia.

Cited by 28 publications

References 13 publications

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

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

Cholinesterase Inhibitors as Adjunctive Therapy in Patients with Schizophrenia and Schizoaffective Disorder

Cholinergic Circuits and Signaling in the Pathophysiology of Schizophrenia

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