Determination of tacrine hydrochloride in human serum by chloroform extraction, reversed-phase high-performance liquid chromatography and fluorimetric detection

Forsyth, Duncan R.; Ford, J. Gair; Truman, Carol; Roberts, Clive J.; Wilcock, GK

doi:10.1016/s0378-4347(00)80620-9

Cited by 25 publications

(11 citation statements)

References 5 publications

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“…On the basis of their findings, the authors concluded that enhanced monoamine transmitter release is unlikely to be involved in any beneficial effect of tacrine in the treatment of Alzheimer's dementia. However, we observed enhancement of SI release of radioactivity from [3H]-noradrenaline-labelled rabbit pulmonary artery preparations with concentrations of tacrine as low as 1 pmol/L, although this concentration is still somewhat higher than the steady state tacrine plasma concentrations of about 0.25 pmol/ L reported from clinical trials with the drug in patients with Alzheimer's dementia (Forsyth et al 1988;Nyback ef al. 1988;Baldwin et al 1991).…”

Section: Discussioncontrasting

confidence: 47%

Prejunctional Actions of Tacrine on Autonomic Neuroeffector Transmission in Rabbit Isolated Pulmonary Artery and Rat Isolated Atria

Fabiani

Kabo

Story

1992

Clin Exp Pharma Physio

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1. This study investigated the effects of tacrine (1,2,3,4-tetrahydro-9-aminoacridine) on the resting and stimulation-induced (SI) release of radioactive substances from isolated preparations of rat atria and rabbit pulmonary artery in which the noradrenergic transmitter stores had been labelled with [3H]-noradrenaline, and from rat atrial preparations in which cholinergic transmitter stores had been labelled with [3H]-acetylcholine. In addition, the effect of tacrine on the uptake of [3H]-noradrenaline by noradrenergic nerves in rat atria was determined. 2. Tacrine produced concentration-dependent increases in the resting efflux of radioactivity from both the [3H]-noradrenaline-loaded artery and atrial preparations. Blockade of neuronal amine transport with desipramine reduced the release of radioactivity evoked by tacrine from atria but not that evoked from artery preparations. Inhibition of monoamine oxidase by pargyline pretreatment markedly reduced the tacrine-evoked release of radioactivity in both atrial and artery preparations. 3. The radioactivity released from [3H]-noradrenaline-labelled rat atrial preparations by 30 mumol/L tacrine consisted entirely of the deaminated metabolite [3H]-DOPEG. The evoked release of [3H]-DOPEG from atria was reduced by approximately 50% by desipramine (1 mumol/L). When atrial monoamine oxidase had been inhibited by pargyline treatment in vivo and in vitro, 30 mumol/L tacrine evoked the release of [3H]-noradrenaline instead of [3H]-DOPEG. However, the amounts of [3H]-noradrenaline released by tacrine when monoamine oxidase was inhibited were only about 25% of the amounts of [3H]-DOPEG released in untreated atria. 4. Tacrine, in concentrations of 1 and 10 mumol/L, enhanced the release of radioactivity evoked by field stimulation of [3H]-noradrenaline-loaded rabbit pulmonary artery preparations. This effect was unaltered by desipramine or pretreatment with pargyline. However, in artery preparations pretreated with pargyline, a high concentration of tacrine (100 mumol/L) markedly reduced SI efflux. In contrast to the findings with artery preparations, tacrine (1-30 mumol/L) did not alter SI efflux in rat atrial preparations. 5. It is concluded that tacrine displaces noradrenaline from intraneuronal transmitter stores of sympathetically-innervated tissues, and that the displaced amine is totally metabolized by monoamine oxidase before leaving the nerve terminals. When deamination of neuronal cytoplasmic noradrenaline is prevented, only a portion of the noradrenaline displaced from storage vesicles passes to the extracellular space. It is likely that the transfer of cytoplasmic noradrenaline out of the terminals is limited by the activity of the amine transport mechanism.

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Section: Discussioncontrasting

confidence: 47%

Prejunctional Actions of Tacrine on Autonomic Neuroeffector Transmission in Rabbit Isolated Pulmonary Artery and Rat Isolated Atria

Fabiani

Kabo

Story

1992

Clin Exp Pharma Physio

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“….-) Macmillan Press Ltd, 1991 THA concentrations were determined by a modification of the high performance liquid chromatography (h.p.l.c.) method of Forsyth et al (1988). Dialysis samples, plasma extracts and tissue extracts were injected directly into a 250 x 4.6mm Hypersil ODS (5pm) column with a Spheri-5 RP18 guard column, and eluted with 33% methanol in H20 containing 1% triethylamine pH 5.0 at a flow rate of 1.0 ml min-'.…”

Section: Animalsmentioning

confidence: 99%

Measurements of tacrine and monoamines in brain by in vivo microdialysis argue against release of monoamines by tacrine at therapeutic doses

Baldwin¹,

Souza²,

Sarna³

et al. 1991

British J Pharmacology

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1 The concentration of tacrine (tetrahydroaminoacridine or THA) in plasma, regions of brain and cerebral extracellular fluid has been studied in the rat at various times following injection of a dose of Smgkg -, i.p. 2 The peak plasma THA concentration was 2.46nmolml-', and occurred 30min post injection and clearance was first order (t1,2 = 90min). The concentration in the brain peaked between 30-60min, and was around 30 times plasma concentration (striatum peak concentration = 65 + 3 nmol g-1). Extracellular cerebral concentration measured by in vivo microdialysis was similar to plasma concentration with-the peak occurring 100 min post-injection. 3 No evidence was obtained by in vivo dialysis for THA inducing dopamine release from striatum or 5-hydroxytryptamine (5-HT) release from the frontal cortex. Enhanced release of dopamine did occur after (+)-amphetamine (5 mgkg ',i.p.) injection, while KCI (100mM) in the probe released both dopamine and 5-HT. 4 Since the minimum plasma THA concentration achieved in this study was at least twice that found in the plasma of patients given THA for the treatment of dementia, these results suggest that monoamine release in the brain does not occur during therapy.

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“…Several articles describe high-perfomance liquid chromatographic (HPLC) methods for the analysis of plasma concentrations of THA alone, using either ultraviolet [9,10] or uorescence detection [11,12]. Other articles describe the HPLC determination of tacrine and its metabolites in human plasma and urine using¯uorescence or ultraviolet detection [12±14].…”

Section: Introductionmentioning

confidence: 99%

Electrochemical Characterization of Tacrine, an Antialzheimer's Disease Drug, and Its Determination in Pharmaceuticals

et al. 2000

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Tacrine, 9-amino-1,2,3,4-tetrahydroacridine, an antialzheimer's disease agent was electrochemically studied and a polarographic method for its quantitative determination in pharmaceuticals was developed. Tacrine was electrochemically reduced and oxidized in aqueous medium, but for analytical purposes the cathodic behavior was prefered. According to the linear relation between the peak current and the tacrine concentration a differential pulse polarographic method was developed. Precision and accuracy of the developed method was checked by recovery studies. The proposed method was applied to the individual capsule assay (ICA) of the commercial capsules, showing that the uniformity content requirements were ful®lled. Alternatively a UV spectroscopic characterization was conducted, from the pH dependence of the absorbance bands an apparent pK a of 10.44 was obtained. For comparative purposes a spectrophotometric determination also was developed.

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Determination of tacrine hydrochloride in human serum by chloroform extraction, reversed-phase high-performance liquid chromatography and fluorimetric detection

Cited by 25 publications

References 5 publications

Prejunctional Actions of Tacrine on Autonomic Neuroeffector Transmission in Rabbit Isolated Pulmonary Artery and Rat Isolated Atria

Prejunctional Actions of Tacrine on Autonomic Neuroeffector Transmission in Rabbit Isolated Pulmonary Artery and Rat Isolated Atria

Measurements of tacrine and monoamines in brain by in vivo microdialysis argue against release of monoamines by tacrine at therapeutic doses

Electrochemical Characterization of Tacrine, an Antialzheimer's Disease Drug, and Its Determination in Pharmaceuticals

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