QuickView for Protriptyline (compound)

Summary
General Info

PubChem

PubChem Compound 14667

Name:	Protriptyline
PubChem Compound ID:	14667
Description:	Tricyclic antidepressant similar in action and side effects to IMIPRAMINE. It may produce excitation.
Molecular formula:	C₁₉H₂₂ClN
Molecular weight:	299.837 g/mol
Synonyms:	438-60-8; MK-240; Vivactil; 5H-Dibenzo(a,d)cycloheptene-5-propanamine, N-methyl-, hydrochloride; EINECS 214-956-3; Triptil Hydrochloride; 5H-DIBENZO(a,d)CYCLOHEPTEN-5-PROPYLAMINE, N-METHYL-, HYDROCHLORIDE; 5H-Dibenzo(a,d)cycloheptene-5-propylamine, N-methyl-, hydrochloride (8CI); Protriptyline hydrochloride; Triptyl. show more » 438-60-8; MK-240; Vivactil; 5H-Dibenzo(a,d)cycloheptene-5-propanamine, N-methyl-, hydrochloride; EINECS 214-956-3; Triptil Hydrochloride; 5H-DIBENZO(a,d)CYCLOHEPTEN-5-PROPYLAMINE, N-METHYL-, HYDROCHLORIDE; 5H-Dibenzo(a,d)cycloheptene-5-propylamine, N-methyl-, hydrochloride (8CI); Protriptyline hydrochloride; Triptyl; N-Methyl-5H-dibenzo(a,d)cycloheptene-5-propylamine hydrochloride; Maximed; 5-(3-Methylaminopropyl)-5H-dibenzo(a,d)cycloheptene hydrochloride; MK-240 (VAN); Normethyl EX4442; Protriptyline hydrochloride [USAN]; Triptil (VAN); 1225-55-4; Concordin; NSC 169912 show less «

DrugBank

Identification

Name:	Protriptyline
Name (isomeric):	DB00344
Drug Type:	small molecule
Description:	Tricyclic antidepressant similar in action and side effects to IMIPRAMINE. It may produce excitation.
Synonyms:	Protryptyline
Brand:	Impril, Vivactil, Norpramin, Aventyl, Novotriptyn, Apo-Trimip, Anafranil, Triptil, Amimetilina, Rhotrimine, Asendin, Apo-Imipramine, Novo-Doxepin, Levate, Apo-Amitriptyline, Novo-Tripramine, Triadapin 5, Surmontil, Sinequan, Tofranil, Pertofrane, Novopramine
Category:	Norepinephrine-Reuptake Inhibitors, Adrenergic Uptake Inhibitors, Antidepressive Agents, Antidepressive Agents, Tricyclic
CAS number:	438-60-8

Pharmacology

Indication:	For the treatment of depression.
Pharmacology:	Protriptyline is a tricyclic antidepressant. It was thought that tricyclic antidepressants work by inhibiting the reuptake of the neurotransmitters norepinephrine and serotonin by nerve cells. However, this response occurs immediately, yet mood does not lift for approximately two weeks. It is now thought that changes occur in receptor sensitivity i... show more » Protriptyline is a tricyclic antidepressant. It was thought that tricyclic antidepressants work by inhibiting the reuptake of the neurotransmitters norepinephrine and serotonin by nerve cells. However, this response occurs immediately, yet mood does not lift for approximately two weeks. It is now thought that changes occur in receptor sensitivity in the cerebral cortex and hippocampus. The hippocampus is part of the limbic system, a part of the brain involved in emotions. Presynaptic receptors are affected: α₁ and β₁ receptors are sensitized, α₂ receptors are desensitised (leading to increased noradrenaline production). Tricyclics are also known as effective analgesics for different types of pain, especially neuropathic or neuralgic pain. A precise mechanism for their analgesic action is unknown, but it is thought that they modulate anti-pain opioid systems in the CNS via an indirect serotonergic route. They are also effective in migraine prophylaxis, but not in abortion of acute migraine attack. The mechanism of their anti-migraine action is also thought to be serotonergic. show less «
Mechanism of Action:	Protriptyline acts by decreasing the reuptake of norepinephrine and serotonin (5-HT).
Route of elimination:	Cumulative urinary excretion during 16 days accounted for approximately 50% of the drug. The fecal route of excretion did not seem to be important.
Toxicity:	Side effects include anxiety, blood disorders, confusion, decreased libido, dizziness, flushing, headache, impotence, insomnia, low blood pressure, nightmares, rapid or irregular heartbeat, rash, seizures, sensitivity to sunlight, stomach and intestinal discomfort, sedation, hypotension, blurred vision, dry mouth, constipation, urinary retention, postural hypotension, tachycardia, hypertension, ECG changes, heart failure, impaired memory and delirium, and precipitation of hypomanic or manic episodes in bipolar depression. Withdrawal symptoms include gastrointestinal disturbances, anxiety, and insomnia.
Affected organisms:	Humans and other mammals

Interactions

Drug interaction:

Triprolidine	Triprolidine and Protriptyline, 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.
Grepafloxacin	Increased risk of cardiotoxicity and arrhythmias
Trospium	Trospium and Protriptyline, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Terbutaline	The tricyclic antidepressant, protriptyline, increases the sympathomimetic effect of terbutaline.
Clonidine	The tricyclic antidepressant, protriptyline, decreases the effect of clonidine.

Triprolidine	Triprolidine and Protriptyline, 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.
Grepafloxacin	Increased risk of cardiotoxicity and arrhythmias
Trospium	Trospium and Protriptyline, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Terbutaline	The tricyclic antidepressant, protriptyline, increases the sympathomimetic effect of terbutaline.
Clonidine	The tricyclic antidepressant, protriptyline, decreases the effect of clonidine.
Tacrine	The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Protriptyline, 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.
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.
Atazanavir	Atazanavir may increase the effect and toxicity of the tricyclic antidepressant, protriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of protriptyline if atazanavir if initiated, discontinued or dose changed.
Butalbital	Barbiturates such as butalbital may increase the metabolism of tricyclic antidepressants such as protriptyline. 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.
Venlafaxine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Terbinafine	Terbinafine may reduce the metabolism and clearance of Protriptyline. Consider alternate therapy or monitor for therapeutic/adverse effects of Protriptyline if Terbinafine is initiated, discontinued or dose changed.
Lumefantrine	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Donepezil	Possible antagonism of action
Orciprenaline	The tricyclic antidepressant, protriptyline, increases the sympathomimetic effect of orciprenaline.
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).
Tramadol	Tramadol increases the risk of serotonin syndrome and seizures.
Guanethidine	The tricyclic antidepressant, protriptyline, decreases the effect of guanethidine.
Epinephrine	The tricyclic antidepressant, protriptyline, increases the sympathomimetic effect of epinephrine.
Fluvoxamine	The SSRI, fluvoxamine, may increase the serum concentration of the tricyclic antidepressant, protriptyline, 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 protriptyline if fluvoxamine is initiated, discontinued or dose changed.
Trazodone	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Desvenlafaxine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Phenylpropanolamine	The tricyclic antidepressant, protriptyline, increases the sympathomimetic effect of phenylpropanolamine.
Phenylephrine	The tricyclic antidepressant, protriptyline, increases the sympathomimetic effect of phenylephrine.
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.
Phenelzine	Possibility of severe adverse effects
Zolmitriptan	Use of two serotonin modulators, such as zolmitriptan and protriptyline, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
Vorinostat	Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Fluoxetine	The SSRI, fluoxetine, may increase the serum concentration of the tricyclic antidepressant, protriptyline, 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 protriptyline if fluoxetine is initiated, discontinued or dose changed.
Terfenadine	Increased risk of cardiotoxicity and arrhythmias
Moclobemide	Possible severe adverse reaction with this combination
Butabarbital	Barbiturates like butabarbital may increase the metabolism of tricyclic antidepressants like protriptyline. 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.
Galantamine	Possible antagonism of action
Quinidine	Additive QTc-prolonging effects may occur. Quinidine may also increase the serum concentration of the tricyclic antidepressant, protriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of protriptyline if quinidine is initiated, discontinued or dose changed. Monitor for the development of torsades de pointes during concomitant therapy.
Rifabutin	The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, protriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of protriptyline if rifabutin is initiated, discontinued or dose changed.
Ziprasidone	Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
Artemether	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Tacrolimus	Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Rifampin	The rifamycin, rifampin, may decrease the effect of the tricyclic antidepressant, protriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of protriptyline if rifampin is initiated, discontinued or dose changed.
Trimethobenzamide	Trimethobenzamide and Protriptyline, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
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.
Cimetidine	Cimetidine may increase the effect of tricyclic antidepressant, protriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of trimipramine if cimetidine is initiated, discontinued or dose changed.
Pseudoephedrine	The tricyclic antidepressant, protriptyline, increases the sympathomimetic effect of pseudoephedrine.
Isocarboxazid	Possibility of severe adverse effects
Fenoterol	The tricyclic antidepressant, protriptyline, increases the sympathomimetic effect of fenoterol.
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.
Rasagiline	Possibility of severe adverse effects
Cisapride	Increased risk of cardiotoxicity and arrhythmias
Voriconazole	Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

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Targets

Sodium-dependent noradrenaline transporter

Sodium-dependent serotonin transporter

Enzymes

Cytochrome P450 2D6

Transporters

Multidrug resistance protein 1