L-Deprenyl in Alzheimerʼs disease: preliminary evidence for behavioral change with monoamine oxidase B inhibition

Pn, Tariot; Rm, Cohen; Sunderland, Trey; Newhouse, PA; Young, Daniel A.; Mellow, AM; Weingartner, Herbert; Ea, Mueller; Dl, Murphy

doi:10.1097/00002093-198701040-00035

Cited by 15 publications

(22 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The role of MAO B in emotional regulation is further supported by a host of clinical studies, showing that chronic administration of l -deprenyl exerts mood-enhancing and anxiolytic effects in depression (Mendlewicz and Youdim, 1980; Quitkin et al , 1984; Robinson et al , 2007) and other disorders (Goad et al , 1991; Tariot et al , 1987; Tolbert and Fuller, 1996). Interestingly, l -deprenyl (both in acute and chronic administration) elicits only minor or no anxiolytic-like effects in rodents (Commissaris et al , 1995; De Angelis and Furlan, 2000; Nowakowska et al , 2001).…”

Section: Discussionmentioning

confidence: 97%

Behavioral Disinhibition and Reduced Anxiety-like Behaviors in Monoamine Oxidase B-Deficient Mice

Bortolato

Godar

Davarian

et al. 2009

Neuropsychopharmacol

View full text Add to dashboard Cite

Monoamine oxidase (MAO) B catalyzes the degradation of b-phenylethylamine (PEA), a trace amine neurotransmitter implicated in mood regulation. Although several studies have shown an association between low MAO B activity in platelets and behavioral disinhibition in humans, the nature of this relation remains undefined. To investigate the impact of MAO B deficiency on the emotional responses elicited by environmental cues, we tested MAO B knockout (KO) mice in a set of behavioral assays capturing different aspects of anxiety-related manifestations, such as the elevated plus maze, defensive withdrawal, marble burying, and hole board. Furthermore, MAO B KO mice were evaluated for their exploratory patterns in response to unfamiliar objects and risk-taking behaviors. In comparison with their wild-type (WT) littermates, MAO B KO mice exhibited significantly lower anxiety-like responses and shorter latency to engage in risk-taking behaviors and exploration of unfamiliar objects. To determine the neurobiological bases of the behavioral differences between WT and MAO B KO mice, we measured the brain-regional levels of PEA in both genotypes. Although PEA levels were significantly higher in all brain regions of MAO B KO in comparison with WT mice, the most remarkable increments were observed in the striatum and prefrontal cortex, two key regions for the regulation of behavioral disinhibition. However, no significant differences in transcript levels of PEA's selective receptor, trace amine-associated receptor 1 (TAAR1), were detected in either region. Taken together, these results suggest that MAO B deficiency may lead to behavioral disinhibition and decreased anxiety-like responses partially through regional increases of PEA levels.

show abstract

Section: Discussionmentioning

confidence: 97%

Behavioral Disinhibition and Reduced Anxiety-like Behaviors in Monoamine Oxidase B-Deficient Mice

Bortolato

Godar

Davarian

et al. 2009

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…The abnormally increased MAO B catalytic activity may produce toxic products, such as H 2 O 2 , therefore these data support an important role for glucocorticoids in the increase in brain MAO B associated with neurodegenerative diseases and mental disorders. In contrast, the MAO B inhibitors, deprenyl (selegiline) and Azilect® (rasagiline), have been used in the therapy of neurodegenerative diseases such as Parkinson’s Disease (Paterson et al 1997; Tatton et al 2000; Maruyama et al 2001; Fernandez and Chen 2007), depression (Goodnick 2007; Robinson and Amsterdam 2007), and senile dementia (Tariot et al 1987; Youdim et al 2005a; Youdim 2006). However, whether these drugs can also protect neurons from glucocorticoids-induced toxicity has never been studied.…”

Section: Discussionmentioning

confidence: 99%

Comparative Neuroprotective Effects of Rasagiline and Aminoindan with Selegiline on Dexamethasone-Induced Brain Cell Apoptosis

Tazik

Johnson

et al. 2009

Neurotox Res

View full text Add to dashboard Cite

Stress can affect the brain and lead to depression; however, the molecular pathogenesis is unclear. An association between stress and stress-induced hypersecretion of glucocorticoids occurs during stress. Dexamethasone (a synthetic glucocorticoid steroid) has been reported to induce apoptosis and increase the activity of monoamine oxidase (MAO) (Youdim et al. 1989). MAO is an enzyme for the degradation of aminergic neurotransmitters; dopamine, noradrenaline and serotonin and dietary amines and MAO inhibitors are classical antidepressant drugs. In this study, we have compared the ability of rasagiline (Azilect) and its main metabolite, R-aminoindan with selegiline (Deprenyl) in prevention of dexamethasone-induced brain cell death employing human neuroblastoma SH-SY5Y cells and glioblastoma 1242-MG cells. Dexamethasone reduced cell viability as measured by MTT test, but rasagiline, selegiline, and 1-R-aminoindan could significantly prevent dexamethasone- © Springer Science+Business Media, LLC 2009Correspondence to: Xiao-Ming Ou, xou@psychiatry.umsmed.edu. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript induced brain cell death. Among three drugs, rasagiline had the highest neuroprotective effect. Furthermore, the inhibitory effects of these drugs on MAOB catalytic activity and on apoptotic DNA damage (TUNEL staining) were examined. Rasagiline exhibited highest inhibition on MAO B enzymatic activity and prevention on DNA damage as compared to selegiline and 1-R-aminoindan. In summary, the greater neuroprotective effect of rasagiline may be associated with the combination of the parent drug and its metabolite 1-R-aminoindan.

show abstract

“…The reasons for this were various, namely the absence of a placebo control group (Martini et al, 1987;Campi et al, 1990;Falsaperla et al, 1990;Monteverde et al, 1990;Goad et al, 1991;Martignoni et al, 1991;Schneider et al, 1991;Alhainen, 1994) non-randomisation (Tariot et al, 1987;Tariot et al, 1988), and confounding medication, e.g. other cholinergic agonists administered to a subset of patients (Schneider et al, 1993;Marin et al, 1995).…”

Section: Studies Included and Excludedmentioning

confidence: 99%

The effect of selegiline in the treatment of people with Alzheimer's disease: a meta‐analysis of published trials

Wilcock

Birks

Whitehead

et al. 2002

Int J Geriat Psychiatry

View full text Add to dashboard Cite

show abstract

L-Deprenyl in Alzheimerʼs disease: preliminary evidence for behavioral change with monoamine oxidase B inhibition

Cited by 15 publications

References 0 publications

Behavioral Disinhibition and Reduced Anxiety-like Behaviors in Monoamine Oxidase B-Deficient Mice

Behavioral Disinhibition and Reduced Anxiety-like Behaviors in Monoamine Oxidase B-Deficient Mice

Comparative Neuroprotective Effects of Rasagiline and Aminoindan with Selegiline on Dexamethasone-Induced Brain Cell Apoptosis

The effect of selegiline in the treatment of people with Alzheimer's disease: a meta‐analysis of published trials

Contact Info

Product

Resources

About