TY - JOUR
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
UR - http://www.scopus.com/inward/record.url?scp=0024971838&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0024971838&partnerID=8YFLogxK
U2 - 10.1016/0304-3940(89)90837-9
DO - 10.1016/0304-3940(89)90837-9
M3 - Article
C2 - 2616041
AN - SCOPUS:0024971838
SN - 0304-3940
VL - 107
SP - 313
EP - 317
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 1-3
ER -