Tetrahydroaminoacridine inhibits human and rat brain monoamine oxidase

Abdu Adem; Sukhwinder S. Jossan; Lars Oreland

doi:10.1016/0304-3940(89)90837-9

Tetrahydroaminoacridine inhibits human and rat brain monoamine oxidase

Abdu Adem
, Sukhwinder S. Jossan
, Lars Oreland

Research output: Contribution to journal › Article › peer-review

45 Citations (Scopus)

Abstract

The inhibitory effects of 1,2,3,4-tetrahydro-9-aminoacridine (THA) on monoamine oxidase (MAO; EC 1.4.3.4) enzyme activities in human hippocampal and rat striatal homogenates have been studied. The activities of MAO-A and MAO-B were estimated radiochemically, in-vitro, in human hippocampus and rat striatum in the presence of various concentrations of THA with [2-¹⁴C]hydroxytryptamine binoxalate (100 μM) and β-[ethyl-¹⁴C]phenylethylamine hydrochloride (20 μM) as substrates for the respective enzyme form. THA was found to inhibit both MAO-A and MAO-B activities reversibly and competitively, with inhibition constants (K_i) of 12.5 μM and > 500 μM respectively, of the rat striatal enzymes. From this it can be extrapolated that at therapeutic tissue concentrations of THA (10^-8 to 10^-6 M), more than 20% of the MAO-A activity should be inhibited. Thus it is possible that inhibition of MAO may be involved in the therapeutic action of THA in Alzheimer's disease.

Original language	English
Pages (from-to)	313-317
Number of pages	5
Journal	Neuroscience Letters
Volume	107
Issue number	1-3
DOIs	https://doi.org/10.1016/0304-3940(89)90837-9
Publication status	Published - Dec 15 1989
Externally published	Yes

Keywords

Enzyme activity
Human brain
MAO-A
MAO-B
Monoamine oxidase
Tetrahydroaminoacridine

ASJC Scopus subject areas

General Neuroscience

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10.1016/0304-3940(89)90837-9

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title = "Tetrahydroaminoacridine inhibits human and rat brain monoamine oxidase",

abstract = "The inhibitory effects of 1,2,3,4-tetrahydro-9-aminoacridine (THA) on monoamine oxidase (MAO; EC 1.4.3.4) enzyme activities in human hippocampal and rat striatal homogenates have been studied. The activities of MAO-A and MAO-B were estimated radiochemically, in-vitro, in human hippocampus and rat striatum in the presence of various concentrations of THA with [2-14C]hydroxytryptamine binoxalate (100 μM) and β-[ethyl-14C]phenylethylamine hydrochloride (20 μM) as substrates for the respective enzyme form. THA was found to inhibit both MAO-A and MAO-B activities reversibly and competitively, with inhibition constants (Ki) of 12.5 μM and > 500 μM respectively, of the rat striatal enzymes. From this it can be extrapolated that at therapeutic tissue concentrations of THA (10-8 to 10-6 M), more than 20\% of the MAO-A activity should be inhibited. Thus it is possible that inhibition of MAO may be involved in the therapeutic action of THA in Alzheimer's disease.",

keywords = "Enzyme activity, Human brain, MAO-A, MAO-B, Monoamine oxidase, Tetrahydroaminoacridine",

author = "Abdu Adem and Jossan, \{Sukhwinder S.\} and Lars Oreland",

note = "Funding Information: This study was supported by grants from the Hans and Loo Osterman's Foundation, Stiftelse f6r Gamla Tj\textasciitilde{}narinnor, Nobel Medica and the Greta and Johan Kochs Foundation. The co-operation of Ass. Prof. Agneta Nordberg and Prof. Bengt Win-blad is acknowledged.",

year = "1989",

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doi = "10.1016/0304-3940(89)90837-9",

language = "English",

volume = "107",

pages = "313--317",

journal = "Neuroscience Letters",

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T1 - Tetrahydroaminoacridine inhibits human and rat brain monoamine oxidase

AU - Adem, Abdu

AU - Jossan, Sukhwinder S.

AU - Oreland, Lars

N1 - Funding Information: This study was supported by grants from the Hans and Loo Osterman's Foundation, Stiftelse f6r Gamla Tj~narinnor, Nobel Medica and the Greta and Johan Kochs Foundation. The co-operation of Ass. Prof. Agneta Nordberg and Prof. Bengt Win-blad is acknowledged.

PY - 1989/12/15

Y1 - 1989/12/15

N2 - The inhibitory effects of 1,2,3,4-tetrahydro-9-aminoacridine (THA) on monoamine oxidase (MAO; EC 1.4.3.4) enzyme activities in human hippocampal and rat striatal homogenates have been studied. The activities of MAO-A and MAO-B were estimated radiochemically, in-vitro, in human hippocampus and rat striatum in the presence of various concentrations of THA with [2-14C]hydroxytryptamine binoxalate (100 μM) and β-[ethyl-14C]phenylethylamine hydrochloride (20 μM) as substrates for the respective enzyme form. THA was found to inhibit both MAO-A and MAO-B activities reversibly and competitively, with inhibition constants (Ki) of 12.5 μM and > 500 μM respectively, of the rat striatal enzymes. From this it can be extrapolated that at therapeutic tissue concentrations of THA (10-8 to 10-6 M), more than 20% of the MAO-A activity should be inhibited. Thus it is possible that inhibition of MAO may be involved in the therapeutic action of THA in Alzheimer's disease.

AB - The inhibitory effects of 1,2,3,4-tetrahydro-9-aminoacridine (THA) on monoamine oxidase (MAO; EC 1.4.3.4) enzyme activities in human hippocampal and rat striatal homogenates have been studied. The activities of MAO-A and MAO-B were estimated radiochemically, in-vitro, in human hippocampus and rat striatum in the presence of various concentrations of THA with [2-14C]hydroxytryptamine binoxalate (100 μM) and β-[ethyl-14C]phenylethylamine hydrochloride (20 μM) as substrates for the respective enzyme form. THA was found to inhibit both MAO-A and MAO-B activities reversibly and competitively, with inhibition constants (Ki) of 12.5 μM and > 500 μM respectively, of the rat striatal enzymes. From this it can be extrapolated that at therapeutic tissue concentrations of THA (10-8 to 10-6 M), more than 20% of the MAO-A activity should be inhibited. Thus it is possible that inhibition of MAO may be involved in the therapeutic action of THA in Alzheimer's disease.

KW - Enzyme activity

KW - Human brain

KW - MAO-A

KW - MAO-B

KW - Monoamine oxidase

KW - Tetrahydroaminoacridine

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VL - 107

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EP - 317

JO - Neuroscience Letters

JF - Neuroscience Letters

IS - 1-3

ER -

Tetrahydroaminoacridine inhibits human and rat brain monoamine oxidase

Abstract

Keywords

ASJC Scopus subject areas

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