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Amitriptyline

Discussion in 'Drug Articles' started by Ilsa, Mar 2, 2012.

  1. Ilsa

    Ilsa Platinum Member & Advisor

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    Amitriptyline (Elavil, Endep, Saroten, Sarotex, Redomex, Adepril, Amineurin, Domical, Euplit, Laroxyl, Lentizol, Miketorin, Triptizol, Tryptanol, Tryptizol) is one of the most frequently used tricyclic antidepressants. Its effects are mediated notably by increasing serotonin and norepinephrine concentrations in the brain. However, other modes of action are likely to contribute to its antidepressant effects as well. This pharmacological profile is also why, beyond its use for treating mood disorders, it can be beneficial for the treatment of nerve and neuropathic pain. It has practically no value as a recreational drug.

    [h="1"]Introduction to [VAR]PAGENAME[/VAR][/h]
    [imgr=white]https://drugs-forum.com/forum/attachment.php?attachmentid=21386&d=1310507590[/imgr]

    [h="1"]Using [VAR]PAGENAME[/VAR][/h]

    [h="2"]Ways of Administration[/h]
    [h="3"]Oral [VAR]PAGENAME[/VAR][/h]
    Oral use is the most common form of administration for Amitryptyline, and it is normally provided in 10mg, 25mg, or 50mg pills. Other routes of administration would appear to be pointless, as it has no recreational value.

    [h="3"]Insufflating [VAR]PAGENAME[/VAR][/h]

    [h="3"]Injecting [VAR]PAGENAME[/VAR][/h]

    [h="3"]Plugging [VAR]PAGENAME[/VAR][/h]

    [h="2"]Effects of [VAR]PAGENAME[/VAR] [/h]

    [h="2"][VAR]PAGENAME[/VAR] combinations[/h]

    [h="2"]Different Uses for [VAR]PAGENAME[/VAR][/h]
    Amitryptyline is sometimes prescribed for sleep disorders in the UK when other drugs have been found to be ineffective.


    [h="1"]Pharmacology of [VAR]PAGENAME[/VAR][/h]

    [h="2"]General[/h]

    Amitriptyline is a Serotonin-Norepinephrine reuptake inhibitor. It also is a negative allosteric modulator at the PCP site of the NMDA receptor.

    LD[sub]50[/sub] (mg/kg) :
    Mice : 350 orally, 65 intraperitoneal
    Rat : 380 orally, 75 intraperitoneal

    [h="2"]Targets, Enzymes, and Transporters[/h]

    [h="3"]Targets[/h]
    Target
    1
    Action
    2
    3 Sodium-dependent noradrenaline transporter Inhibitor[FOOTNOTE=1][NOPARSE]Vaishnavi SN, Nemeroff CB, Plott SJ, Rao SG, Kranzler J, Owens MJ: Milnacipran: a comparative analysis of human monoamine uptake and transporter binding affinity. Biol Psychiatry. 2004 Feb 1;55(3):320-2.[/NOPARSE][/FOOTNOTE][FOOTNOTE=2][NOPARSE]Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58.[/NOPARSE][/FOOTNOTE]
    4 Sodium-dependent serotonin transporter Inhibitor[FOOTNOTE=3][NOPARSE]Gould GG, Altamirano AV, Javors MA, Frazer A: A comparison of the chronic treatment effects of venlafaxine and other antidepressants on serotonin and norepinephrine transporters. Biol Psychiatry. 2006 Mar 1;59(5):408-14. Epub 2005 Sep 2.[/NOPARSE][/FOOTNOTE][FOOTNOTE=4][NOPARSE]Troelsen KB, Nielsen EO, Mirza NR: Chronic treatment with duloxetine is necessary for an anxiolytic-like response in the mouse zero maze: the role of the serotonin transporter. Psychopharmacology (Berl). 2005 Oct;181(4):741-50. Epub 2005 Sep 29.[/NOPARSE][/FOOTNOTE][FOOTNOTE=1][/FOOTNOTE][FOOTNOTE=5][NOPARSE]Ushijima K, Sakaguchi H, Sato Y, To H, Koyanagi S, Higuchi S, Ohdo S: Chronopharmacological study of antidepressants in forced swimming test of mice. J Pharmacol Exp Ther. 2005 Nov;315(2):764-70. Epub 2005 Aug 3.[/NOPARSE][/FOOTNOTE][FOOTNOTE=6][NOPARSE]Kalia M: Neurobiological basis of depression: an update. Metabolism. 2005 May;54(5 Suppl 1):24-7.[/NOPARSE][/FOOTNOTE][FOOTNOTE=2][/FOOTNOTE][FOOTNOTE=7][NOPARSE]Werling LL, Keller A, Frank JG, Nuwayhid SJ: A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: treatment of involuntary emotional expression disorder. Exp Neurol. 2007 Oct;207(2):248-57. Epub 2007 Jun 30.[/NOPARSE][/FOOTNOTE]
    5 5-hydroxytryptamine receptor 1A Inhibitor[FOOTNOTE=8][NOPARSE]Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65.[/NOPARSE][/FOOTNOTE]
    6 5-hydroxytryptamine receptor 2A Inhibitor[FOOTNOTE=8][/FOOTNOTE]
    7 Delta-type opioid receptor Agonist[FOOTNOTE=9][NOPARSE]Onali P, Dedoni S, Olianas MC: Direct agonist activity of tricyclic antidepressants at distinct opioid receptor subtypes. J Pharmacol Exp Ther. 2010 Jan;332(1):255-65. Epub 2009 Oct 14.[/NOPARSE][/FOOTNOTE]
    8 Kappa-type opioid receptor Agonist[FOOTNOTE=9][/FOOTNOTE]
    9 High affinity nerve growth factor receptor Agonist[FOOTNOTE=10][NOPARSE]Jang SW, Liu X, Chan CB, Weinshenker D, Hall RA, Xiao G, Ye K: Amitriptyline is a TrkA and TrkB receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity. Chem Biol. 2009 Jun 26;16(6):644-56.[/NOPARSE][/FOOTNOTE]
    10 BDNF/NT-3 growth factors receptor Agonist[FOOTNOTE=10][/FOOTNOTE]
    11 Alpha-1A adrenergic receptor Antagonist[FOOTNOTE=8][/FOOTNOTE][FOOTNOTE=11][NOPARSE]Nojimoto FD, Mueller A, Hebeler-Barbosa F, Akinaga J, Lima V, Kiguti LR, Pupo AS: The tricyclic antidepressants amitriptyline, nortriptyline and imipramine are weak antagonists of human and rat alpha1B-adrenoceptors. Neuropharmacology. 2010 Jul-Aug;59(1-2):49-57. Epub 2010 Apr 2.[/NOPARSE][/FOOTNOTE]
    12 Alpha-1D adrenergic receptor Antagonist[FOOTNOTE=11][/FOOTNOTE]
    13 Alpha-2A adrenergic receptor Antagonist[FOOTNOTE=8][/FOOTNOTE][FOOTNOTE=12][NOPARSE]Ozdogan UK, Lahdesmaki J, Mansikka H, Scheinin M: Loss of amitriptyline analgesia in alpha 2A-adrenoceptor deficient mice. Eur J Pharmacol. 2004 Feb 6;485(1-3):193-6.[/NOPARSE][/FOOTNOTE]
    14 Histamine H1 receptor Antagonist[FOOTNOTE][/FOOTNOTE]
    15 Muscarinic acetylcholine receptor M1 Antagonist[FOOTNOTE=8][/FOOTNOTE]
    16 Muscarinic acetylcholine receptor M2 Antagonist[FOOTNOTE=8][/FOOTNOTE]
    17 Muscarinic acetylcholine receptor M3 Antagonist[FOOTNOTE=8][/FOOTNOTE]
    18 Muscarinic acetylcholine receptor M4 Antagonist[FOOTNOTE=8][/FOOTNOTE]
    19 Muscarinic acetylcholine receptor M5 Antagonist[FOOTNOTE=8][/FOOTNOTE]
    20 Potassium voltage-gated channel subfamily KQT member 2 Inhibitor[FOOTNOTE=13][NOPARSE]Punke MA, Friederich P: Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels. Anesth Analg. 2007 May;104(5):1256-64, tables of contents. [/NOPARSE][/FOOTNOTE]
    21 Potassium voltage-gated channel subfamily A member 1 Inhibitor[FOOTNOTE=13][/FOOTNOTE]
    22 Potassium voltage-gated channel subfamily D member 2 Inhibitor[FOOTNOTE=14][NOPARSE]Casis O, Sanchez-Chapula JA: Disopyramide, imipramine, and amitriptyline bind to a common site on the transient outward K+ channel. J Cardiovasc Pharmacol. 1998 Oct;32(4):521-6.[/NOPARSE][/FOOTNOTE]
    23 Potassium voltage-gated channel subfamily D member 3 Inhibitor[FOOTNOTE=14][/FOOTNOTE]
    24 Histamine H2 receptor Blocker[FOOTNOTE=15][NOPARSE]Angus JA, Black JW: Pharmacological assay of cardiac H2-receptor blockade by amitriptyline and lysergic acid diethylamide. Circ Res. 1980 Jun;46(6 Pt 2):I64-9.[/NOPARSE][/FOOTNOTE]
    25 Histamine H4 receptor Binder[FOOTNOTE=16][NOPARSE]Nguyen T, Shapiro DA, George SR, Setola V, Lee DK, Cheng R, Rauser L, Lee SP, Lynch KR, Roth BL, O’Dowd BF: Discovery of a novel member of the histamine receptor family. Mol Pharmacol. 2001 Mar;59(3):427-33.[/NOPARSE][/FOOTNOTE]
    26 Sigma non-opioid intracellular receptor 1 Agonist[FOOTNOTE=17][NOPARSE]Villard V, Meunier J, Chevallier N, Maurice T: Pharmacological interaction with the sigma1 (sigma1)-receptor in the acute behavioral effects of antidepressants. J Pharmacol Sci. 2011;115(3):279-92.[/NOPARSE][/FOOTNOTE][FOOTNOTE=7][/FOOTNOTE]
    27 5-hydroxytryptamine receptor 2C Binder[FOOTNOTE=18][NOPARSE]Di Matteo V, De Blasi A, Di Giulio C, Esposito E: Role of 5-HT receptors in the control of central dopamine function. Trends Pharmacol Sci. 2001 May;22(5):229-32.[/NOPARSE][/FOOTNOTE]
    28 Alpha-1B adrenergic receptor Antagonist[FOOTNOTE=11][/FOOTNOTE]
    29 5-hydroxytryptamine receptor 7 Antagonist[FOOTNOTE=19][NOPARSE]Lucchelli A, Santagostino-Barbone MG, D’Agostino G, Masoero E, Tonini M: The interaction of antidepressant drugs with enteric 5-HT7 receptors. Naunyn Schmiedebergs Arch Pharmacol. 2000 Sep;362(3):284-9.[/NOPARSE][/FOOTNOTE]
    30 5-hydroxytryptamine receptor 1D Binder[FOOTNOTE=7][/FOOTNOTE]
    31 Mu-type opioid receptor Binder[FOOTNOTE=20][NOPARSE]Wahlstrom A, Lenhammar L, Ask B, Rane A: Tricyclic antidepressants inhibit opioid receptor binding in human brain and hepatic morphine glucuronidation. Pharmacol Toxicol. 1994 Jul;75(1):23-7.[/NOPARSE][/FOOTNOTE][FOOTNOTE=21][NOPARSE]Hamon M, Gozlan H, Bourgoin S, Benoliel JJ, Mauborgne A, Taquet H, Cesselin F, Mico JA: Opioid receptors and neuropeptides in the CNS in rats treated chronically with amoxapine or amitriptyline. Neuropharmacology. 1987 Jun;26(6):531-9.[/NOPARSE][/FOOTNOTE]
    32 5-hydroxytryptamine receptor 1B Binder[FOOTNOTE=7][/FOOTNOTE]
    33 5-hydroxytryptamine receptor 6 Antagonist[FOOTNOTE=22][NOPARSE]Kohen R, Metcalf MA, Khan N, Druck T, Huebner K, Lachowicz JE, Meltzer HY, Sibley DR, Roth BL, Hamblin MW: Cloning, characterization, and chromosomal localization of a human 5-HT6 serotonin receptor. J Neurochem. 1996 Jan;66(1):47-56.[/NOPARSE][/FOOTNOTE][FOOTNOTE=23][NOPARSE]Sebben M, Ansanay H, Bockaert J, Dumuis A: 5-HT6 receptors positively coupled to adenylyl cyclase in striatal neurones in culture. Neuroreport. 1994 Dec 20;5(18):2553-7.[/NOPARSE][/FOOTNOTE]
    34 Potassium voltage-gated channel subfamily KQT member 3 Blocker[FOOTNOTE=13][/FOOTNOTE]
    35 Beta-1 adrenergic receptor Binder[FOOTNOTE=7][/FOOTNOTE]
    36 Beta-2 adrenergic receptor Binder[FOOTNOTE=7][/FOOTNOTE]
    37 Beta-3 adrenergic receptor Binder[FOOTNOTE=7][/FOOTNOTE]
    [FOOTNOTE=24][NOPARSE]DrugBank: a knowledgebase for drugs, drug actions and drug targets. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M.Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6.[/NOPARSE][/FOOTNOTE]

    [h="3"]Enzymes[/h]
    Enzyme
    1
    Short Name
    2
    Action
    3
    Action
    4
    5 Cytochrome P450 1A2[FOOTNOTE=27][/FOOTNOTE][FOOTNOTE=29][/FOOTNOTE][FOOTNOTE=30][/FOOTNOTE][FOOTNOTE=33][NOPARSE]Information Hyperlinked Over Proteins (iHOP) – Website[/NOPARSE][/FOOTNOTE][FOOTNOTE=31][/FOOTNOTE][FOOTNOTE=32][/FOOTNOTE] CYP1A2 Substrate
    6 Cytochrome P450 2B6[FOOTNOTE=31][/FOOTNOTE][FOOTNOTE=32][/FOOTNOTE] CYP2B6 Substrate
    7 Cytochrome P450 2C8[FOOTNOTE=31][/FOOTNOTE][FOOTNOTE=32][/FOOTNOTE] CYP2C8 Substrate Inhibitor
    8 Cytochrome P450 2C9[FOOTNOTE=28][/FOOTNOTE][FOOTNOTE=29][/FOOTNOTE][FOOTNOTE=30][/FOOTNOTE][FOOTNOTE=31][/FOOTNOTE][FOOTNOTE=32][/FOOTNOTE] CYP2C9 Substrate
    9 Cytochrome P450 2C19[FOOTNOTE=33][NOPARSE]Shin JG, Park JY, Kim MJ, Shon JH, Yoon YR, Cha IJ, Lee SS, Oh SW, Kim SW, Flockhart DA: Inhibitory effects of tricyclic antidepressants (TCAs) on human cytochrome P450 enzymes in vitro: mechanism of drug interaction between TCAs and phenytoin. Drug Metab Dispos. 2002 Oct;30(10):1102-7.[/NOPARSE][/FOOTNOTE][FOOTNOTE=29][/FOOTNOTE][FOOTNOTE=30][/FOOTNOTE][FOOTNOTE=31][/FOOTNOTE][FOOTNOTE=32][/FOOTNOTE] CYP2C19 Substrate Inhibitor
    10 Cytochrome P450 2D6[FOOTNOTE=26][NOPARSE]Baumann P: Pharmacokinetic-pharmacodynamic relationship of the selective serotonin reuptake inhibitors. Clin Pharmacokinet. 1996 Dec;31(6):444-69.[/NOPARSE][/FOOTNOTE][FOOTNOTE=27][NOPARSE]Wen B, Ma L, Zhu M: Bioactivation of the tricyclic antidepressant amitriptyline and its metabolite nortriptyline to arene oxide intermediates in human liver microsomes and recombinant P450s. Chem Biol Interact. 2008 May 9;173(1):59-67. Epub 2008 Feb 14.[/NOPARSE][/FOOTNOTE][FOOTNOTE=28][NOPARSE]Ghahramani P, Ellis SW, Lennard MS, Ramsay LE, Tucker GT: Cytochromes P450 mediating the N-demethylation of amitriptyline. Br J Clin Pharmacol. 1997 Feb;43(2):137-44.[/NOPARSE][/FOOTNOTE][FOOTNOTE=29]Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1.[/FOOTNOTE][FOOTNOTE=30]Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.[/FOOTNOTE][FOOTNOTE=31]Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24.[/FOOTNOTE][FOOTNOTE=32][NOPARSE]Venkatakrishnan K, von Moltke LL, Greenblatt DJ: Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther. 2001 Apr;297(1):326-37.[/NOPARSE][/FOOTNOTE] CYP2D6 Substrate Inhibitor
    11 Cytochrome P450 2E1[FOOTNOTE=31][/FOOTNOTE] CYP2E1 Substrate Inhibitor
    12 Cytochrome P450 3A4[FOOTNOTE=27][/FOOTNOTE][FOOTNOTE=28][/FOOTNOTE][FOOTNOTE=29][/FOOTNOTE][FOOTNOTE=31][/FOOTNOTE][FOOTNOTE=32][/FOOTNOTE] CYP3A4 Substrate
    13 Cytochrome P450 3A5[FOOTNOTE=27][/FOOTNOTE] CYP3A5 Substrate
    [FOOTNOTE=24][/FOOTNOTE]


    [h="3"]Transporters[/h]
    Transporter
    1
    Action
    2
    3 TBC To Be Continued (WIP)




    [h="1"]Chemistry of [VAR]PAGENAME[/VAR][/h]
    Property
    1
    Values
    2
    3 Systematic(IUPAC) name: 3-(10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-ylidene)-N,N-dimethyl-1-propanamine
    4 Synonyms: 5-(3-dimethylaminopropylidene)dibenzo[a,d][1,4]cycloheptadiene, 10,11-dihydro-N,N-dimethyl-5H-dibenzo[a,d]cycloheptene-[Delta]^5,[gamma]-propylamine, 5-([gamma]-dimethylaminopropylidene)-5H-dibenzo[a,d]-10,11-dihydrocycloheptene, 10,11-dihydro-5-([gamma]-dimethylaminopropylidene)-5H-dibenzo[a,d]cycloheptene ; Elavil, Endep, Saroten, Sarotex, Redomex, Adepril, Amineurin, Domical, Euplit, Laroxyl, Lentizol, Miketorin, Triptizol, Tryptanol, Tryptizol (hydrochloride)
    5 Molecular Formula: C[sub]20[/sub]H[sub]23[/sub]N
    6 Molar mass: 277.403 g/mol; 313.87 g/mol (hydrochloride)
    7 CAS Registry Number: 50-48-6; 549-18-8 (hydrochloride)
    8 Melting Point: 196-197℃ (hydrochloride)
    9 Boiling Point: no data
    10 Flash Point: no data
    11 Solubility: Freely soluble in water, chloroform, alcohol (ethanol). Insoluble in ether.
    12 Additionnal data: pKa 9.4
    [FOOTNOTE=25]Merck Index, Fifteenth Edition[/FOOTNOTE]

    [h="1"]The Dangers of [VAR]PAGENAME[/VAR][/h]
    [h=“2”]General Warnings[/h]

    [h="2"]Side Effects and Interactions[/h]

    [h=“3”]Potential Side Effects[/h]

    [h=“3”]Potential Drug Interactions[/h]
    Note this is not a comprehensive list of potential interactions, but commonly known interactions. You should check with your medical provider for additional information.
    AS OF DATE: 22 April 2015

    Drug
    1
    Effects
    2
    3 Altretamine Risk of severe hypotension
    4 Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
    5 Atazanavir Atazanavir may increase the effect and toxicity of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if atazanavir if initiated, discontinued or dose changed.
    6 Butabarbital Barbiturates like butabarbital may increase the metabolism of tricyclic antidepressants like amitriptyline. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
    7 Butalbital Barbiturates such as butalbital may increase the metabolism of tricyclic antidepressants such as amitriptyline. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
    8 Carbamazepine Carbamazepine may decrease the serum concentration of the tricyclic antidepressant, amitriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if carbamazepine is initiated, discontinued or dose changed.
    9 Cimetidine Cimetidine may increase the effect of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if cimetidine is initiated, discontinued or dose changed.
    10 Cisapride Increased risk of cardiotoxicity and arrhythmias
    11 Clonidine The tricyclic antidepressant, amitriptyline, decreases the effect of clonidine.
    12 Desvenlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
    13 Dihydroquinidine barbiturate Dihydroquinidine barbiturate increases the effect of the tricyclic antidepressant, amitriptyline.
    14 Dobutamine The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect, dobutamine.
    15 Donepezil Possible antagonism of action
    16 Dopamine The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect, dopamine.
    17 Duloxetine Possible increase in the levels of this agent when used with duloxetine
    18 Ephedra The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of ephedra.
    19 Ephedrine The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of ephedrine.
    20 Epinephrine The tricyclic antidepressant, amitriptyline, may increase the sympathomimetic effect of epinephrine.
    21 Fenoterol The tricyclic antidepressant, amitriptyline, may increase the sympathomimetic effect of fenoterol.
    22 Fluconazole Fluconazole may increase the effect and toxicity of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Additive QTc-prolonging effects may also occur. Monitor for changes in the therapeutic and adverse effects of amitriptyline if fluconazole is initiated, discontinued or dose changed. Monitor for the development of torsades de pointes during concomitant therapy.
    23 Fluoxetine The SSRI, fluoxetine, may increase the serum concentration of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of amitriptyline if fluoxetine is initiated, discontinued or dose changed.
    24 Fluvoxamine The SSRI, fluvoxamine, may increase the serum concentration of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of amitriptyline if fluvoxamine is initiated, discontinued or dose changed.
    25 Galantamine Possible antagonism of action
    26 Grepafloxacin Increased risk of cardiotoxicity and arrhythmias
    27 Guanethidine The tricyclic antidepressant, amitriptyline, decreases the effect of guanethidine.
    28 Indacaterol Concomitant therapy with monoamine oxidase inhibitors, tricyclic antidepressants, or other drugs that prolong the QTc interval should be monitored closely. These drugs may potentiate the effect of adrenergic agonist on the cardiovascular system.
    29 Iobenguane May diminish the therapeutic effect and increase chances of producing a false negative imaging result of Iobenguane as it inhibits noradrenaline transporter function
    30 Isocarboxazid Possibility of severe adverse effects
    31 Isoprenaline The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of isoproterenol.
    32 Ketoconazole Ketoconazole, a moderate CYP2D6 inhibitor, may increase the serum concentration of amitriptyline by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if ketoconazole is initiated, discontinued or dose changed.
    33 Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
    34 Mephentermine The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of mephentermine.
    35 Mesoridazine Increased risk of cardiotoxicity and arrhythmias
    36 Metaraminol The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of metaraminol.
    37 Methoxamine The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of methoxamine.
    38 Moclobemide Possible severe adverse reaction with this combination
    39 Norepinephrine The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of norepinephrine.
    40 Orciprenaline The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of orciprenaline.
    41 Phenelzine Possibility of severe adverse effects
    42 Phenylephrine The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of phenylephrine.
    43 Phenylpropanolamine The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of phenylpropanolamine.
    44 Pirbuterol The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of pirbuterol.
    45 Procaterol The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of procaterol.
    46 Pseudoephedrine The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of pseudoephedrine.
    47 Quinidine Additive QTc-prolonging effects may occur. Quinidine may also increase the serum concentration of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if quinidine is initiated, discontinued or dose changed. Monitor for the development of torsades de pointes during concomitant therapy.
    48 Quinidine barbiturate Quinidine barbiturate increases the effect of tricyclic antidepressant, amitriptyline.
    49 Rasagiline Possibility of severe adverse effects
    50 Rifabutin The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, amitriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if rifabutin is initiated, discontinued or dose changed.
    51 Rifampicin The rifamycin, rifampin, may decrease the effect of the tricyclic antidepressant, amitriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if rifampin is initiated, discontinued or dose changed.
    52 Ritonavir Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if ritonavir if initiated, discontinued or dose changed.
    53 Rivastigmine Possible antagonism of action
    54 Salbutamol The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of salbutamol.
    55 Sibutramine Increased risk of CNS adverse effects
    56 Sparfloxacin Increased risk of cardiotoxicity and arrhythmias
    57 Tacrine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Amitriptyline, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
    58 Tacrolimus Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
    59 Terbinafine Terbinafine may reduce the metabolism and clearance of Amitryptyline. Consider alternate therapy or monitor for therapeutic/adverse effects of Amytriptyline if Terbinafine is initiated, discontinued or dose changed.
    60 Terbutaline The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of terbutaline.
    61 Terfenadine Increased risk of cardiotoxicity and arrhythmias
    62 Thioridazine Increased risk of cardiotoxicity and arrhythmias
    63 Thiothixene May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
    64 Toremifene Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
    65 Tramadol Tramadol increases the risk of serotonin syndrome and seizures.
    66 Tranylcypromine Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.
    67 Trazodone Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
    68 Trimethobenzamide Trimethobenzamide and Amitriptyline, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
    69 Trimipramine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
    70 Triprolidine Triprolidine and Amitriptyline, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
    71 Trospium Trospium and Amitriptyline, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
    72 Venlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
    73 Vilazodone Monitor for toxic effects of tricyclic antidepressants if a selective serotonin reuptake inhibitor (SSRI) is initiated or the dose is increased. The influence of the SSRI may take several days or weeks to be fully realized or resolved.
    74 Voriconazole Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
    75 Vorinostat Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
    76 Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
    77 Zolmitriptan Use of two serotonin modulators, such as zolmitriptan and amitriptyline, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
    78 Zuclopenthixol Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
    [FOOTNOTE=24][/FOOTNOTE]

    [h=“3”]Potential Food Interactions and Precautions[/h]
    • Avoid taking with alcohol.
    • Avoid excessive quantities of coffee or tea (caffeine).
    • Avoid St. John's Wort.
    • Take with food to reduce irritation.
    [FOOTNOTE=24][/FOOTNOTE]


    [h="1"]Producing [VAR]PAGENAME[/VAR][/h]


    [h="1"]Forms of [VAR]PAGENAME[/VAR][/h]


    [h="1"]Legal Status of [VAR]PAGENAME[/VAR][/h]

    [h="2"]United Nations[/h]

    [h="2"]Australia[/h]
    Amitriptyline is a Schedule 4 substance and is only available by prescription.
    Brand name is Endep, however there are generic versions available.

    [h="2"]EU[/h]

    [h="2"]Norway[/h]
    Available only by prescription.

    [h="2"]USA[/h]
    Amitriptyline (Elavil) is unscheduled in the United States. Available only by prescription. This means that sales and distribution are allowed only by those with a license and only to those with a prescription (according to FDA regulations). Possession of Amitriptyline is not illegal without prescription.


    [h="1"]History of [VAR]PAGENAME[/VAR][/h]

    [H="2"]Popularity of [VAR]PAGENAME[/VAR] over time[/H]
    [insights][VAR]PAGENAME[/VAR][/insights]

    [h="1"]More [VAR]PAGENAME[/VAR] Sections[/h]


    [h="1"]The Latest [VAR]PAGENAME[/VAR] Threads[/h]

    [showthreads=10]<insert forumid of the drugs forum>[/showthreads]


    [cat]Antidepressants[/cat]
    [cat]Tricyclic Antidepressant[/cat]

    [h="1"]References[/h]
    [REFLIST][/REFLIST]
     

    Attached Files:

  2. C.D.rose

    C.D.rose Donating

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    Another first. ;)

    I extended the introduction a little, just so that the article isn't completely blank. I was wondering about my reference to amitriptyline's mode of action as "increasing 5HT and NE concentrations in the brain". It's vague and technically even false, but I didn't want to use more complicated language for the introduction section. Maybe someone can come up with a wording that is both correct and not too complicated...
     
  3. stayupandplay

    stayupandplay Silver Member

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    The Federal Bureau of Prisons in the USA dispenses amitriptyline for a a host of prisoner medical issues. I have to admit it works surprisingly well...at least for myself and others I've spoken to about this drug. We called them "greenies" as the caps were a strange shade of green. I'm aware "greenies" is a label that was given to dexadrine years ago, but we went with it anyway.
    If someone couldn't sleep....greenies. If there was pain or inflamation.....greenies. It was also added to a persons regimen of psych meds. I know some folks that snorted the caps. There is a lot of filler as well as amit in those caps. It caused drowsiness is all.
     
  4. C.D.rose

    C.D.rose Donating

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    Hmm, amitriptyline for sleep makes sense. For pain, it could make sense, but it's probably not neuropathic pain that most prisoners get treated for. I can also imagine that snorting it may give some drowsy or drugged-like feeling, but I don't think that anyone outside of prison would consider amitriptyline a worthy recreational drug. (Of course, except for the 1 in 10000 or so. Some people also snort bupropion, etc.)

    If you have sources for the use of amitriptyline in prison, feel free to add something to the article. If you can't edit Wiki articles, just post the info plus the sources in here.

    And by the way, you have the most gory avatar I have ever seen. ;)
     
  5. AllAroundTheLight

    AllAroundTheLight Silver Member

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    I don't claim to know a lot about this particular substance other than that it is an older type of antideppresant. What interests me about it is that my favorite musician of all time died from an overdose of this drug. nick drake used it to kill himself
     
  6. C.D.rose

    C.D.rose Donating

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    Yes, amitriptyline is pretty dangerous in an overdose. That's one of the reasons why TCAs and this one in particular are not considered first-line treatments. They are too effective to take them off the market though.
     
  7. Baba Blacksheep

    Baba Blacksheep Titanium Member

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    A doctor prescribed this for restless leg syndrome and sleep disorder. Didn't like it much so swapped it for diazepam. Did a much better job.
     
  8. C.D.rose

    C.D.rose Donating

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    Please note that this thread is for the discussion of questions concerning the wiki article. Discussion of amitriptyline itself should take place here or in any other regular thread dealing with aspects of amitriptyline use.
     
  9. John_bob

    John_bob Titanium Member

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    Filled chem data, There's still a need for some editing of the table because it's not sexy right now. But the data is here.
     
  10. Damocles

    Damocles Titanium Member

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    Added targets, lots of footnotes, and cleaned up existing footnotes.

    Will get back to the other stuff soon.

    Damocles added 137 Minutes and 21 Seconds later...

    Added lots of information - possible drug interactions, food precautions, and enzymes.

    Still work in process.
     
    Last edited: Apr 23, 2015
  11. NorthQueensland

    NorthQueensland Silver Member

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    Elaborated more on the scheduling of the drug in Australia as well as suggested that there are generic versions available.