Terfenadine, a Nonsedating Antihistamine

Carter, C A; Wojciechowski, Norbert J.; Hayes, James M.; Skoutakis, Vasilios A.; Rickman, Lucy A.

doi:10.1177/106002808501901103

Cited by 16 publications

(4 citation statements)

References 10 publications

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“…We concluded the increase in excitability due to optogenetic stimulation can be reverted by terfenadine. This could be due to blockage of baseline conductances, such as ERG channels or other targets like histamine1, kir 6, and Kv11.1 ( Carter et al, 1985 ).…”

Section: Resultsmentioning

confidence: 99%

Intrinsic excitability mechanisms of neuronal ensemble formation

Alejandre-García

Kim

Pérez-Ortega

et al. 2022

eLife

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Neuronal ensembles are coactive groups of cortical neurons, found in spontaneous and evoked activity, that can mediate perception and behavior. To understand the mechanisms that lead to the formation of ensembles, we co-activated layer 2/3 pyramidal neurons in brain slices from mouse visual cortex, in animals of both sexes, replicating in vitro an optogenetic protocol to generate ensembles in vivo. Using whole-cell and perforated patch-clamp pair recordings we find that, after optogenetic or electrical stimulation, coactivated neurons increase their correlated activity, a hallmark of ensemble formation. Coactivated neurons showed small biphasic changes in presynaptic plasticity, with an initial depression followed by a potentiation after a recovery period. Optogenetic and electrical stimulation also induced significant increases in frequency and amplitude of spontaneous EPSPs, even after single-cell stimulation. In addition, we observed unexpected strong and persistent increases in neuronal excitability after stimulation, with increases in membrane resistance and reductions in spike threshold. A pharmacological agent that blocks changes in membrane resistance can revert this effect. These significant increases in excitability may partly generate the observed biphasic synaptic plasticity. We propose that cell-intrinsic changes in excitability are involved in the formation of neuronal ensembles. We propose an 'iceberg' model, by which increased neuronal excitability makes subthreshold connections suprathreshold, enhancing the effect of already existing synapses, and generating a new neuronal ensemble.

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Section: Resultsmentioning

confidence: 99%

Intrinsic excitability mechanisms of neuronal ensemble formation

Alejandre-García

Kim

Pérez-Ortega

et al. 2022

eLife

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“…The substance does not impair psychomotor performance to a similar extent as traditional antihistamines [4,[6][7][8]. Besides blocking the H1 receptor, Terfenadine may interfere with degranulation of mast cells and thus decrease histamine release [5].…”

Section: Introductionmentioning

confidence: 99%

Stimulating Effect of Terfenadine on Erythrocyte Cell Membrane Scrambling

Signoretto

Castagna²,

Bhuyan³

et al. 2016

Cell Physiol Biochem

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Background/Aims: The antihistaminic drug Terfenadine may trigger apoptosis of tumor cells, an effect unrelated to its effect on histamine receptors. Similar to apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal death of erythrocytes characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Signaling triggering eryptosis include increase of cytosolic Ca²⁺ activity ([Ca²⁺]_i), oxidative stress, and ceramide. The present study explored, whether Terfenadine is capable to trigger eryptosis. Methods: Flow cytometry was employed to estimate phosphatidylserine abundance at the erythrocyte surface from annexin-V-binding, cell volume from forward scatter, [Ca²⁺]_i from Fluo3-fluorescence, abundance of reactive oxygen species (ROS) from 2′,7′-dichlorodihydrofluorescein (DCF) diacetate dependent fluorescence, and ceramide abundance at the human erythrocyte surface utilizing specific antibodies. Hemolysis was quantified from haemoglobin concentration in the supernatant. Results: A 48 hours exposure of human erythrocytes to Terfenadine (≥ 5 µM) significantly increased the percentage of annexin-V-binding cells and triggered hemolysis without significantly modifying the average forward scatter. Terfenadine (7.5 µM) significantly increased Fluo3-fluorescence, but did not significantly modify DCF fluorescence or ceramide abundance. The effect of Terfenadine on annexin-V-binding was significantly blunted but not abolished by removal of extracellular Ca²⁺. Exposure of human erythrocytes to Ca²⁺ ionophore ionomycin (1 µM, 15 min) triggered annexin-V-binding, an effect augmented by Terfenadine pretreatment (10 µM, 48 hours). Conclusions: Terfenadine triggers phospholipid scrambling of the human erythrocyte cell membrane, an effect in part due to entry of extracellular Ca²⁺ and in part due to sensitizing human erythrocyte cell membrane scrambling to Ca²⁺.

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“…The reliability of the methods was established by parallel determination against the official USP method. The procedures described were successfully applied to the determination of the bulk drug and its pharmaceutical formulations by applying the standard addition technique.Key words: terfenadine determination, spectrophotometry, chromotropic acid, mono-and bis-azo compounds.* To whom correspondence should be addressed Terfenadine, 1-(4-tert-butylphenyl)-4-[4-(c~-hydroxybenzhydryl) piperidin] butan-l-ol [50679-08-8], is a specific non-sedating antagonist of histamine receptors which is devoid of central nervous activity in both animals and human [1]. The antihistamine profile of terfenadine along with its pharmacodynamic properties and therapeutic efficiency were reviewed [2].…”

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confidence: 99%

Utility of the ion-pair formation for spectrophotometric determination of terfenadine in pure form and in some pharmaceutical formulations

Amin

Issa

1999

Mikrochim Acta

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Abstract.A spectrophotometric procedure for the determination of terfenadine and a number of its pharmaceutical preparations has been developed that offers advantages of simplicity, rapidity, sensitivity and stability indication over the official USP (1995) method. The proposed method is based on the formation of ion-pairs by the reaction of terfenadine with some chromotropic acid mono-and bis-azo dyes. Different variables affecting the ion-pair formation were studied and optimized. At the maximum absorption of 557, 521,592 and 543 nm, Beer's law is obeyed in the range 0.2-18.6, 0.2-16.4, 0.2-25.0 and 0.2-22.2 lag m1-1 on using reagents I, II, III and IV, respectively. The stoichiometxic ratio and stability of each ion-pair were estimated and the mechanism of the reaction is discussed. The molar absorptivity and Sandell sensitivity of the produced ion-pairs were calculated in addition to Ringbom optimum concentration ranges. Statistical treatment of the experimental results indicates that the procedures are precise and accurate. Excipients used as additives in pharmaceutical formulations did not interfere in the proposed procedures. The reliability of the methods was established by parallel determination against the official USP method. The procedures described were successfully applied to the determination of the bulk drug and its pharmaceutical formulations by applying the standard addition technique.Key words: terfenadine determination, spectrophotometry, chromotropic acid, mono-and bis-azo compounds.* To whom correspondence should be addressed Terfenadine, 1-(4-tert-butylphenyl)-4-[4-(c~-hydroxybenzhydryl) piperidin] butan-l-ol [50679-08-8], is a specific non-sedating antagonist of histamine receptors which is devoid of central nervous activity in both animals and human [1]. The antihistamine profile of terfenadine along with its pharmacodynamic properties and therapeutic efficiency were reviewed [2]. The fate of the drug in the body was followed by measuring its plasma concentration using radioimmuno-assay. The excreted drug in faeces was detected by applying the 14C analysis while the metabolic products in urine were determined by gas chromatography-mass spectrometry [3]. Recently more routine oriented analytical methods using high performance liquid chromatographic [4][5][6][7] and spectrophotometric techniques [8][9][10] were reported. The tacky nature of the terfenadine in most of the organic solvents made the drug solution handling rather difficult resulting in tedious and time consuming procedures. Consequently, more accessible economical routine testing methods for the starting material and dosage forms are appreciated.In a previous work, the ion-pair complex formation methods were described to determine other pharmaceutical drugs [11][12][13][14], but no methods are reported for the determination of terfenadine in pure form and in pharmaceutical formulations depending on this idea.Chromotropic acid (4,5-dihydroxynaphthalene-2,7 disulphonic acid) azo dyes are very famous indicators for the spectroph...

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Terfenadine, a Nonsedating Antihistamine

Cited by 16 publications

References 10 publications

Intrinsic excitability mechanisms of neuronal ensemble formation

Intrinsic excitability mechanisms of neuronal ensemble formation

Stimulating Effect of Terfenadine on Erythrocyte Cell Membrane Scrambling

Utility of the ion-pair formation for spectrophotometric determination of terfenadine in pure form and in some pharmaceutical formulations

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