Differential inhibition of catecholamine secretion by amitriptyline through blockage of nicotinic receptors, sodium channels, and calcium channels in bovine adrenal chromaffin cells

Park, Tae‐Ju; Shin, Soyoung; Suh, Byung‐Chang; Suh, Eunkyung; Lee, Ihn-Soon; Kim, Yong-Sik; Kim, Kyong‐Tai

doi:10.1002/(sici)1098-2396(199807)29:3<248::aid-syn7>3.0.co;2-6

Cited by 46 publications

(10 citation statements)

References 22 publications

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“…Over the past 20 years, several independent groups have reported on the nAChR inhibitory actions of classic tricyclic antidepressants including imipramine, [11][12][13] nortriptyline, amitriptyline, 14,15 and desipramine. 13,16 More recent studies have characterized newer, more selective monoamine reuptake inhibitors including fluoxetine, [17][18][19] sertraline, paroxetine, nefazodone, 20 nisoxetine, citalopram, nomifensine, 21 and GBR-12909 22 as nAChR antagonists.…”

Section: Antidepressants As Nicotinic Acetylcholine Receptor Antagonistssupporting

confidence: 90%

Nicotinic acetylcholine receptors as targets for antidepressants

et al. 2002

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While the monoamine deficiency hypothesis of depression is still most commonly used to explain the actions of antidepressant drugs, a growing body of evidence has accumulated that is not adequately explained by the hypothesis. This article draws attention to contributions from another apparently common pharmacological property of antidepressant medications-the inhibition of nicotinic acetylcholine receptors (nAChR). Evidence is presented suggesting the hypercholinergic neurotransmission, which is associated with depressed mood states, may be mediated through excessive neuronal nicotinic receptor activation and that the therapeutic actions of many antidepressants may be, in part, mediated through inhibition of these receptors. In support of this hypothesis, preliminary evidence is presented suggesting that the potent, centrally acting nAChR antagonist, mecamylamine, which is devoid of monoamine reuptake inhibition, may reduce symptoms of depression and mood instability in patients with comorbid depression and bipolar disorder. If this hypothesis is supported by further preclinical and clinical research, nicotinic acetylcholine receptor antagonists may represent a novel class of therapeutic agents for treating mood disorders.

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Section: Antidepressants As Nicotinic Acetylcholine Receptor Antagonistssupporting

confidence: 90%

Nicotinic acetylcholine receptors as targets for antidepressants

et al. 2002

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“…The effect of nicotine on axonal excitability was reduced by concentrations of amitriptyline of around 1 µM (314 ng·mL −1 ), and this is consistent with a previous report illustrating the high sensitivity of nicotinic responses to amitriptyline (Park et al. , 1998).…”

Section: Discussionsupporting

confidence: 92%

“…, 2003). Interestingly, it has been noted that this effect requires only sub‐micromolar concentrations in contrast to the micromolar concentrations necessary to inhibit voltage‐dependent sodium channels (Park et al. , 1998).…”

Section: Introductionmentioning

confidence: 99%

Low concentrations of amitriptyline inhibit nicotinic receptors in unmyelinated axons of human peripheral nerve

Freysoldt¹,

Fleckenstein²,

Lang³

et al. 2009

British J Pharmacology

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Background and purpose: Amitriptyline is often prescribed as a first-line treatment for neuropathic pain but its precise mode of analgesic action remains uncertain. Amitriptyline is known to inhibit voltage-dependent ion channels and also to act as an antagonist at ligand-gated ion channels, such as nicotinic acetylcholine receptors (nAChRs). In the present study, we tested the effect of amitriptyline on nicotinic responses of unmyelinated axons in isolated segments of human peripheral nerve. In particular, a comparison was made between the concentrations of amitriptyline necessary for inhibition of nAChRs and those required for inhibition of the compound C-fibre action potential. Experimental approach: Isolated axon fascicles were prepared from short segments of human sural nerve, and multiple measures of axonal excitability were recorded using computer-controlled threshold tracking software. Key results: Amitriptyline (EC50 2.6 mM) reduced the nicotine-induced increase in C-fibre excitability but only slightly altered the amplitude and latency to onset of the compound action potential. In contrast, tetrodotoxin produced a clear reduction in the amplitude and a prolongation of action potential onset latency but was without effect on the nicotine-induced increase in axonal excitability. Conclusions and implications:These data demonstrate that low concentrations of amitriptyline suppress the response of human peripheral C-type axons to nicotine by directly inhibiting nAChRs. Blockade of tetrodotoxin-sensitive, voltagedependent sodium channels does not contribute to this effect. An inhibitory action of amitriptyline on nAChRs in unmyelinated nociceptive axons may be an important component of amitriptyline's therapeutic effect in the treatment of neuropathic pain.

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“…Amitriptyline acts on many sites; it blocks Na + , K + , and Ca 2+ voltage‐gated ion channels 15–17 as well as the muscarinic, cholinergic, nicotinic, histaminergic, α 2 ‐adrenergic, opioid, adenosine, and N ‐methyl‐ d ‐aspartate receptors 18–25 . The broad variety of receptors on which amitriptyline acts might explain its superior efficacy, but it is also the cause of the wide array of adverse effects limiting its oral use.…”

Section: Introductionmentioning

confidence: 99%

High Doses of Topical Amitriptyline in Neuropathic Pain: Two Cases and Literature Review

Kopsky¹,

Hesselink²

2011

Pain Practice

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Severe chronic neuropathic pain is a challenge to treat, and due to adverse effects of classical oral medication, optimal and effective dose levels are difficult to reach. Therefore, administration of topical analgesics might be an option, due to reduced adverse effects, and increased patient compliance. The aim of this article is to describe two cases treated effectively with topical amitriptyline 5% and 10%, the highest dosage described to date. The first patient was a 39-year-old man, suffering from severe intractable neuropathic pain in feet and hands, due to diabetes mellitus type II (DM-II). After application of amitriptyline 5% the patient experienced a complete relieve only in the hands, whereas after application of amitriptyline 10%, a total reduction of pain occurred within 20 minutes, lasting the whole day. The second patient was a 57-year-old man, suffering for 10 years from progressive sensory disturbances in both feet and increasing pain due to chronic idiopathic axonal polyneuropathy (CIAP). Amitriptyline 5% cream reduced pain in the toes nearly completely, but this was not the case in the heels. Amitriptyline 10% reduced pain in the feet, however, systemic adverse effects occurred, mainly drowsiness. The patient decided to stop topical treatment because of these adverse effects. These two cases suggest an analgesic dose-response effect of topical amitriptyline in painful neuropathy. Systemic adverse effects should be taken into account.

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Differential inhibition of catecholamine secretion by amitriptyline through blockage of nicotinic receptors, sodium channels, and calcium channels in bovine adrenal chromaffin cells

Cited by 46 publications

References 22 publications

Nicotinic acetylcholine receptors as targets for antidepressants

Nicotinic acetylcholine receptors as targets for antidepressants

Low concentrations of amitriptyline inhibit nicotinic receptors in unmyelinated axons of human peripheral nerve

High Doses of Topical Amitriptyline in Neuropathic Pain: Two Cases and Literature Review

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