Further analysis of the neuropharmacological profile of 9-amino-1,2,3,4-tetrahydroacridine (THA), and alleged drug for the treatment of Alzheimer's disease

Journal Article · Fri Jan 01 00:00:00 EST 1988 · Life Sci.; (United States)

DOI:https://doi.org/10.1016/0024-3205(88)90431-6· OSTI ID:5471576

Drukarch, B; Leysen, J E; Stoof, J C

In a recent study the authors have documented the acetylcholinesterase and outward K+-current inhibiting activity of 9-amino-1,2,3,4-tetrahydroacridine (THA), a drug reportedly active in the treatment of Alzheimer patients. In the present study they have investigated the effects of THA on the uptake and release of radiolabeled NA, DA and 5-HT. THA concentration-dependently inhibited the uptake of these monoamines with IC-50 values of approximately 1, 7 and 2 ..mu..M respectively. Release studies of these radiolabeled monoamines from control and reserpine pretreated tissue revealed that the THA-induced uptake inhibition does not occur at the level of the axonal membrane but at the level of the monoaminergic storage granules. In addition the affinity of THA for alpha-1, alpha-2 and beta-adrenoceptors, for D-2 dopamine, S-la and S-2 serotonin and for muscarinic receptors was investigated. It appeared that in concentrations up to 1 ..mu..M THA did not display any affinity towards these receptors. It is concluded from these experiments that the effects of THA on monoaminergic neurotransmission might contribute to the alleged therapeutic action of THA in Alzheimer's disease. 17 references, 3 figures, 1 table.

• Research Organization: Free Univ., Amsterdam, Netherlands
• OSTI ID: 5471576
• Journal Information: Life Sci.; (United States), Vol. 42:9
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
ACRIDINES
BIOCHEMICAL REACTION KINETICS
DOPAMINE
UPTAKE
NERVOUS SYSTEM DISEASES
CHEMOTHERAPY
NORADRENALINE
SEROTONIN
BIOELECTRICITY
ENZYME ACTIVITY
INHIBITION
RADIOISOTOPES
RECEPTORS
SYMPATHOMIMETICS
TRACER TECHNIQUES
ADRENAL HORMONES
AMINES
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZINES
AZOLES
CARDIOTONICS
CARDIOVASCULAR AGENTS
DISEASES
DRUGS
ELECTRICITY
HETEROCYCLIC COMPOUNDS
HORMONES
HYDROXY COMPOUNDS
INDOLES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MEMBRANE PROTEINS
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHENOLS
POLYPHENOLS
PROTEINS
PYRIDINES
PYRROLES
RADIOPROTECTIVE SUBSTANCES
REACTION KINETICS
STEROID HORMONES
THERAPY
TRYPTAMINES
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