Blockade of a cardiac K+ channel by tacrine: interactions with muscarinic and adenosine receptors

Freeman, Shirley E.; Lau, Wai‐Man; Szilágyi, M.

doi:10.1016/0014-2999(88)90363-9

Cited by 27 publications

(11 citation statements)

References 23 publications

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“…THA has also been reported recently to interact with adenosinergic systems and adenosine A 1 receptors. For example, in vitro studies of the inotropic effects of adenosine and 2-chloroadenosine reveal that 1-4 micromolar THA reversed the negative inotropic effects of these adenosinergic compounds and THA has also been demonstrated to be a weak competitor at adenosine A 1 receptors in guinea-pig brain (Freeman et al 1988). Since in vitro studies reveal that adenosine and some of its more stable analogues can inhibit the release of acetylcholine and monoamines from neuronal preparations (Ginsborg & Hirst, 1972;Harms et al 1978Harms et al , 1979Michaelis et al 1979), inhibition of adenosinergic modulation of acetylcholine or monoamine neurotransmitter release may play a role in the clinical effectiveness of THA in Alzheimer's dementias.…”

Section: Disorders Of Attention and Cognitionmentioning

confidence: 99%

Prospective role for adenosine and adenosinergic systems in psychiatric disorders

Durcan¹,

Morgan²

1990

Psychol. Med.

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Section: Disorders Of Attention and Cognitionmentioning

confidence: 99%

Prospective role for adenosine and adenosinergic systems in psychiatric disorders

Durcan¹,

Morgan²

1990

Psychol. Med.

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“…In addition to the inhibition of cholinesterases, tacrine has also been shown to block certain potassium channels (Osterrieder, 1987;Rogawski, 1987;Stevens and Gotman, 1987;Freeman et al, 1988), to interfere with the binding of specific ligands to muscarinic (Freeman et al, 1988;Flynn and Mash, 1989;Potter et al, 1989;Musilkov~t and Tu~ek, 1991) and nicotinic (Nilsson et al, 1987;Perry et al, 1988) receptors and with the uptake of choline (Buyukuysal and Wurtman, 1989) and of monoamine neurotransmitters (Drukarch et al, 1988) into neurons, to affect the release of acetylcholine (ACh) from the cholinergic nerve terminals (Hallak and Giacobini, 1989;Lindmar and L6ffelholz, 1990;Thesleff etal., 1990;Tu6ek and Dole~al, 1991), and to inhibit the activities of monoamine oxidase (Adem et al, 1989) and cyclic AMP phosphodiesterase (Curley et al, 1984).…”

Section: Introductionmentioning

confidence: 98%

Investigation of the mechanism of the effect of tacrine (tetrahydroaminoacridine) on the metabolism of acetylcholine and choline in brain cortical prisms

Doležal

Tuček

1992

J Neural Transm Gen Sect

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The mechanism by which tacrine increases the content and synthesis of acetylcholine (ACh) in cerebrocortical prisms exposed to an irreversible inhibitor of cholinesterases and incubated under resting conditions (Dolezal and Tucek, 1991) is not known. As found in the present experiments, this effect of tacrine is only apparent if its application had been preceded by a period of preincubation, but the preincubation is ineffective if it occurs in the presence of hemicholinium-3. Apparently, choline or a choline-containing compound accumulates in the slices during the preincubation and is then utilized for the enhanced synthesis of ACh in the presence of tacrine. Tacrine did not induce a decrease in the amount of radiolabel that had been incorporated from choline into acid-insoluble compounds, which suggests that the choline which is used for the synthesis of additional ACh does not originate from choline lipids. However, tacrine was found to diminish the efflux of choline from prisms which had been preincubated with an increased concentration of choline in the medium, and from prisms incubated in the presence of hemicholinium-3. It also diminished the efflux of radioactive choline that had accumulated in the prisms during preincubation with a very low concentration of tacrine, when the prisms were subsequently incubated with 4-aminopyridine. It is proposed that the potency of tacrine to increase the content and synthesis of ACh in cerebrocortical prisms whose cholinesterases had been inhibited is due to its ability to diminish the efflux of endogenous choline from the nerve terminals.

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“…It also interacts with the N-methyl-¿/-aspartate-phencyclidine receptor complex [19], and was found to increase the skeletal protein-protein interac tions in erythrocyte membranes [20]. It has been reported to increase the release of 5-HT, NA, DA [21], and GABA [22], and to interact at high concentrations with the aden osine receptor [23]. There is also a report of an inhibitory action on monoamine oxidase A and B (MAO-A and MAO-B) activity [24].…”

Section: Pharmacological Propertiesmentioning

confidence: 99%

THA – Historical Aspects, Review of Pharmacological Properties and Therapeutic Effects

Soares¹,

Gershon²

1995

Dement Geriatr Cogn Disord

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The authors reviewed historical data in the development of THA, as well as recent data on its pharmacological properties and therapeutic effects on cognitive dysfunction. A medline search was conducted to identify the trials conducted with THA in Alzheimer''s disease (AD) patients. The findings seem to lend support to some palliative action of THA, especially at higher doses, but in these doses about 2/3 of the patients experience significant adverse reactions. The significance of these findings is discussed, with emphasis on the their relevance for the management of AD patients.

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Blockade of a cardiac K+ channel by tacrine: interactions with muscarinic and adenosine receptors

Cited by 27 publications

References 23 publications

Prospective role for adenosine and adenosinergic systems in psychiatric disorders

Prospective role for adenosine and adenosinergic systems in psychiatric disorders

Investigation of the mechanism of the effect of tacrine (tetrahydroaminoacridine) on the metabolism of acetylcholine and choline in brain cortical prisms

THA – Historical Aspects, Review of Pharmacological Properties and Therapeutic Effects

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