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.
Using Amitriptyline
Ways of Administration
Oral Amitriptyline
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.Insufflating Amitriptyline
Injecting Amitriptyline
Plugging Amitriptyline
Effects of Amitriptyline
Amitriptyline combinations
Different Uses for Amitriptyline
Amitryptyline is sometimes prescribed for sleep disorders in the UK when other drugs have been found to be ineffective.
Pharmacology of Amitriptyline
General
Amitriptyline is a Serotonin-Norepinephrine reuptake inhibitor. It also is a negative allosteric modulator at the PCP site of the NMDA receptor.
LD50 (mg/kg) :
Mice : 350 orally, 65 intraperitoneal
Rat : 380 orally, 75 intraperitonealTargets, Enzymes, and Transporters
Targets
[1]
Sodium-dependent noradrenaline transporter Inhibitor[1][2] Sodium-dependent serotonin transporter Inhibitor[3][4][1][5][6][2][7] 5-hydroxytryptamine receptor 1A Inhibitor[8] 5-hydroxytryptamine receptor 2A Inhibitor[8] Delta-type opioid receptor Agonist[9] Kappa-type opioid receptor Agonist[9] High affinity nerve growth factor receptor Agonist[10] BDNF/NT-3 growth factors receptor Agonist[10] Alpha-1A adrenergic receptor Antagonist[8][11] Alpha-1D adrenergic receptor Antagonist[11] Alpha-2A adrenergic receptor Antagonist[8][12] Histamine H1 receptor Antagonist[13] Muscarinic acetylcholine receptor M1 Antagonist[8] Muscarinic acetylcholine receptor M2 Antagonist[8] Muscarinic acetylcholine receptor M3 Antagonist[8] Muscarinic acetylcholine receptor M4 Antagonist[8] Muscarinic acetylcholine receptor M5 Antagonist[8] Potassium voltage-gated channel subfamily KQT member 2 Inhibitor[1] Potassium voltage-gated channel subfamily A member 1 Inhibitor[1] Potassium voltage-gated channel subfamily D member 2 Inhibitor[14] Potassium voltage-gated channel subfamily D member 3 Inhibitor[14] Histamine H2 receptor Blocker[15] Histamine H4 receptor Binder[16] Sigma non-opioid intracellular receptor 1 Agonist[17][7] 5-hydroxytryptamine receptor 2C Binder[18] Alpha-1B adrenergic receptor Antagonist[11] 5-hydroxytryptamine receptor 7 Antagonist[19] 5-hydroxytryptamine receptor 1D Binder[7] Mu-type opioid receptor Binder[20][21] 5-hydroxytryptamine receptor 1B Binder[7] 5-hydroxytryptamine receptor 6 Antagonist[22][23] Potassium voltage-gated channel subfamily KQT member 3 Blocker[1] Beta-1 adrenergic receptor Binder[7] Beta-2 adrenergic receptor Binder[7] Beta-3 adrenergic receptor Binder[7] Enzymes
[1]
Cytochrome P450 1A2[24][25][26][27][28][29] CYP1A2 Substrate Cytochrome P450 2B6[28][29] CYP2B6 Substrate Cytochrome P450 2C8[28][29] CYP2C8 Substrate Inhibitor Cytochrome P450 2C9[30][25][26][28][29] CYP2C9 Substrate Cytochrome P450 2C19[27][25][26][28][29] CYP2C19 Substrate Inhibitor Cytochrome P450 2D6[31][24][30][25][26][28][29] CYP2D6 Substrate Inhibitor Cytochrome P450 2E1[28] CYP2E1 Substrate Inhibitor Cytochrome P450 3A4[24][30][25][28][29] CYP3A4 Substrate Cytochrome P450 3A5[24] CYP3A5 Substrate Transporters
TBC To Be Continued (WIP)
Chemistry of Amitriptyline
[2]
Systematic(IUPAC) name: 3-(10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-ylidene)-N,N-dimethyl-1-propanamine 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) Molecular Formula: C20H23N Molar mass: 277.403 g/mol; 313.87 g/mol (hydrochloride) CAS Registry Number: 50-48-6; 549-18-8 (hydrochloride) Melting Point: 196-197℃ (hydrochloride) Boiling Point: no data Flash Point: no data Solubility: Freely soluble in water, chloroform, alcohol (ethanol). Insoluble in ether. Additionnal data: pKa 9.4
The Dangers of Amitriptyline
General Warnings
Side Effects and Interactions
Potential Side Effects
Potential Drug Interactions
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
[1]
Altretamine Risk of severe hypotension Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided. 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. 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. 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. 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. 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. Cisapride Increased risk of cardiotoxicity and arrhythmias Clonidine The tricyclic antidepressant, amitriptyline, decreases the effect of clonidine. Desvenlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Dihydroquinidine barbiturate Dihydroquinidine barbiturate increases the effect of the tricyclic antidepressant, amitriptyline. Dobutamine The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect, dobutamine. Donepezil Possible antagonism of action Dopamine The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect, dopamine. Duloxetine Possible increase in the levels of this agent when used with duloxetine Ephedra The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of ephedra. Ephedrine The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of ephedrine. Epinephrine The tricyclic antidepressant, amitriptyline, may increase the sympathomimetic effect of epinephrine. Fenoterol The tricyclic antidepressant, amitriptyline, may increase the sympathomimetic effect of fenoterol. 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. 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. 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. Galantamine Possible antagonism of action Grepafloxacin Increased risk of cardiotoxicity and arrhythmias Guanethidine The tricyclic antidepressant, amitriptyline, decreases the effect of guanethidine. 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. Iobenguane May diminish the therapeutic effect and increase chances of producing a false negative imaging result of Iobenguane as it inhibits noradrenaline transporter function Isocarboxazid Possibility of severe adverse effects Isoprenaline The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of isoproterenol. 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. Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided. Mephentermine The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of mephentermine. Mesoridazine Increased risk of cardiotoxicity and arrhythmias Metaraminol The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of metaraminol. Methoxamine The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of methoxamine. Moclobemide Possible severe adverse reaction with this combination Norepinephrine The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of norepinephrine. Orciprenaline The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of orciprenaline. Phenelzine Possibility of severe adverse effects Phenylephrine The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of phenylephrine. Phenylpropanolamine The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of phenylpropanolamine. Pirbuterol The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of pirbuterol. Procaterol The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of procaterol. Pseudoephedrine The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of pseudoephedrine. 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. Quinidine barbiturate Quinidine barbiturate increases the effect of tricyclic antidepressant, amitriptyline. Rasagiline Possibility of severe adverse effects 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. 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. 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. Rivastigmine Possible antagonism of action Salbutamol The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of salbutamol. Sibutramine Increased risk of CNS adverse effects Sparfloxacin Increased risk of cardiotoxicity and arrhythmias 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. Tacrolimus Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution. 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. Terbutaline The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of terbutaline. Terfenadine Increased risk of cardiotoxicity and arrhythmias Thioridazine Increased risk of cardiotoxicity and arrhythmias 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. 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. Tramadol Tramadol increases the risk of serotonin syndrome and seizures. 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. Trazodone Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Trimethobenzamide Trimethobenzamide and Amitriptyline, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects. 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. 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. Trospium Trospium and Amitriptyline, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects. Venlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. 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. Voriconazole Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP). Vorinostat Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP). Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated. 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. 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). Potential Food Interactions and Precautions
Legal Status of Amitriptyline
United Nations
Australia
Amitriptyline is a Schedule 4 substance and is only available by prescription.
Brand name is Endep, however there are generic versions available.EU
Norway
Available only by prescription.USA
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.