프로트리프틸린

164.5 Ų [M+H]+ [CCS Type: DT; Buffer gas: N2; Ionization: ESI+; Dataset: Antidepressants]

162.8 Ų [M+H]+ [CCS Type: TW; Method: Major Mix IMS/Tof Calibration Kit (Waters)]

162.8 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

161.47 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Other interactions that also may potentiate the effects of tricyclic antidepressants can result from interference with their metabolism in the liver. This effect has been associated with neuroleptic drugs, methylphenidate, and certain steroids, including oral contraceptives. /Tricyclic antidepressants/

TRICYCLIC ANTIDEPRESSANTS MAY ENHANCE EFFECTS OF ORAL ANTICOAGULANTS. /TRICYCLIC ANTIDEPRESSANTS/

A PARTICULARLY SEVERE, BUT RARE, DRUG-DRUG INTERACTION HAS BEEN NOTED FOLLOWING THE CONCURRENT ADMINISTRATION OF AN MAO INHIBITOR AND A TRICYCLIC ANTIDEPRESSANT. /TRICYCLIC ANTIDEPRESSANTS/

THIS AGENT IS ALSO CONTRAINDICATED IN PT TAKING ANY OF MAO INHIBITOR ANTIDEPRESSANTS, SUCH AS NIALAMIDE, ISOCARBOXAZID, TRANYLCYPROMINE, OR PHENELZINE. /HYDROCHLORIDE/

For more Interactions (Complete) data for PROTRIPTYLINE (32 total), please visit the HSDB record page.

Protriptyline shares side effects common to all tricyclic antidepressants. The most frequent of these are dry mouth, constipation, urinary retention, increased heart rate, sedation, irritability, dizziness, decreased coordination, 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 problems. Other more complicated side effects include; chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling; sudden numbness or weakness, especially on one side of the body; sudden headache, confusion, problems with vision, speech, or balance; hallucinations, or seizure (convulsions); easy bruising or bleeding, unusual weakness; restless muscle movements in your eyes, tongue, jaw, or neck; urinating less than usual or not at all; extreme thirst with headache, nausea, vomiting, and weakness; or feeling light-headed or fainting. Deaths may occur from overdosage with this class of drugs. Multiple drug ingestion (including alcohol) is common in deliberate tricyclic antidepressant overdose. (Wikipedia)

Liver test abnormalities have been reported to occur in 10% to 12% of patients on tricyclic antidepressants, but elevations are uncommonly above 3 times the upper limit of normal. The aminotransferase abnormalities are usually mild, asymptomatic and transient, reversing even with continuation of medication. The rate of serum enzyme elevations specifically during protriptyline therapy has not been well defined. Rare instances of clinically apparent acute liver injury have been reported in patients on tricyclic antidepressants, but there have been no specific reports related to protriptyline. In typical tricyclic antidepressant acute liver injury, the latency to onset has ranged from 1 to 14 months. The pattern of serum enzyme elevations was typically cholestatic, but hepatocellular cases have also been reported including an acute hepatitis-like syndrome with acute liver failure. Instances of acute cholestatic hepatitis and prolonged jaundice compatible with vanishing bile duct syndrome have been linked to other tricyclic antidepressants, mostly amitriptyline and imipramine, the two most commonly used agents in this class. Signs or symptoms of hypersensitivity (rash, fever and eosinophilia) are frequent in reported cases, but these symptoms are usually mild and transient. Autoantibody formation is rare. Protriptyline is a rarely used tricyclic antidepressant but is suspected of having a profile of adverse effects similar to that of imipramine and amitriptyline.

Protriptyline, like all TCAs, has multiple adverse effects. Although as effective as SSRIs and SNRIs, TCAs, and MAOs are not first-line treatment due to their side effects. Among the TCAs, protriptyline is the most likely to cause tachycardia, hypotension, anxiety, and agitation, and for this reason, some European countries have discontinued protriptyline use.

Tricyclic antidepressants, like all antidepressants, are used in a group of patients that are already at increased risk of attempted suicide. Thus, overdose with such drugs is something that needs to have a plan at hand. Furthermore, TCAs are often used in drug-resistant depression, which makes them even more of a risk than the first-line SSRIs and SNRIs. Thus protriptyline is a very potent TCA and a dangerous drug for overdose.

Protriptyline acts by decreasing the reuptake of norepinephrine and serotonin (5-HT).

OCCASIONAL PT WILL SHOW PHYSICAL DEPENDENCE ... FOLLOWING ABRUPT DISCONTINUATION OF HIGH DOSES ... /TRICYCLIC ANTIDEPRESSANTS/

Effects of overdosage include agitation, hallucinations, hyperreflexia, hyperpyrexia, and convulsions. /Tricyclic antidepressants/

VENTRICULAR FIBRILLATION WAS OBSERVED IN 51-YR OLD WOMAN RECEIVING PERPHENAZINE & PROTRIPTYLINE. PERPHENAZINE ALSO WIDENED VENTRICULAR ECHO ZONE & ALLOWED INDUCTION OF LONG RUNS OF VENTRICULAR TACHYCARDIA. BOTH DRUGS INCR INCIDENCE OF VENTRICULAR DYSRHYTHMIAS.

EFFECTS OF AMITRIPTYLINE-HCL, NORTRIPTYLINE-HCL, & PROTRIPTYLINE HCL & BW-247 ON PERFORMANCE TESTS & SUBJECTIVE RATINGS IN 2 DOUBLE BLIND TRIALS WITH 24 VOLUNTEERS. NO SIGNIFICANT CHANGE FOLLOWED 10 MG PROTRIPTYLINE OR 12.5 & 25 MG BW-247.

PROTRIPTYLINE HAD NO EFFECT ON THE EXTN FRACTION OF WATER.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

protriptyline

DILI Negative

Oral

DOI:10.1016/j.drudis.2019.09.022

POS CHRONOTROPISM IN RATS @ PLASMA CONCN OF 0.04-1.2 MUG/ML; @ HIGHER LEVELS POS CHRONOTROPIC EFFECT DECR & BRADYCARDIA DEVELOPED. THRESHOLD PLASMA LEVEL GIVING 40 DEG RIGHT ROTATION OF ELECTRICAL AXIS OF HEART 1.75 MUG/ML. ATRIOVENTRICULAR CONDUCTION PROLONGED @ 3.6 MUG/ML.

KNOWN OXIDATION OF 10,11 DOUBLE BOND OF PROTRIPTYLINE IN MAN, MINIATURE PIG, & DOG... 2 METABOLITES HAVE BEEN DETECTED WHICH DEMONSTRATE EPOXIDE INTERMEDIATE, NAMELY, DIHYDRODIOL & REARRANGEMENT PRODUCT WHOSE FORMATION IS...CATIONIC INTERMEDIATE...REARRANGING TO DIHYDROANTHRACENIC STRUCTURE.

IN DOGS, MINIATURE PIGS, & MAN, 3 URINARY METABOLITES HAVE NOW BEEN FOUND 10-HYDROXY-N-METHYL-5H-DIBENZO(AD)CYCLOHEPTENE-5-PROPYLAMINE, 10,11-DIHYDROXY-N-METHYL-5H-DIBENZO(AD)CYCLOHEPTENE-5-PROPYLAMINE & 5,10-DIHYDRO-10-FORMYLANTHRACENE-5-PROPYLAMINE.

...PROTRIPTYLINE...AFFORDS URINARY 10,11-OXIDE.

IN URINE OF RATS TREATED WITH PROTRIPTYLINE...2 METABOLITES HAVE BEEN IDENTIFIED...AS 10,11-DIHYDRO-10,11-EPOXY-5-(3-M ETHYLAMINOPROPYL)-5H-DIBENZO[A,D]CYCLOHEPTENE & 10,11-DIHYDRO-10,11-EPOXY-5-(3-AMINOPROPYL)-5H-DIBENZO[A,D]CYCLOHEPTENE.

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.

4NDU154T12

PROTRIPTYLINE

Established Pharmacologic Class [EPC] - Tricyclic Antidepressant

Protriptyline is a Tricyclic Antidepressant.

Substances that contain a fused three-ring moiety and are used in the treatment of depression. These drugs block the uptake of norepinephrine and serotonin into axon terminals and may block some subtypes of serotonin, adrenergic, and histamine receptors. However, the mechanism of their antidepressant effects is not clear because the therapeutic effects usually take weeks to develop and may reflect compensatory changes in the central nervous system.

Drugs that block the transport of adrenergic transmitters into axon terminals or into storage vesicles within terminals. The tricyclic antidepressants (ANTIDEPRESSIVE AGENTS, TRICYCLIC) and amphetamines are among the therapeutically important drugs that may act via inhibition of adrenergic transport. Many of these drugs also block transport of serotonin.

Protriptyline is reported to undergo cumulative urinary excretion during 16 days, which accounts for approximately 50% of the total drug administered. The fecal excretion pathway seems to play a minimal role in drug elimination.

EXCRETION...IS RAPID, IN CONTRAST TO LONG LATENCY OF ONSET OF ACTION OF DRUGS. /TRICYCLIC ANTIDEPRESSANTS/

...WELL ABSORBED FROM GI TRACT. ... RAPIDLY DISTRIBUTED & METABOLIZED BY DEMETHYLATION, OXIDATION, & AROMATIC HYDROXYLATION. /IMIPRAMINE/

IN URINE OF RATS TREATED WITH PROTRIPTYLINE... THERE WAS TWICE AS MUCH 10,11-DIHYDRO-10,11-EPOXY-5-(3-METHYLAMINOPROPYL)-5H-DIBENZO[A,D]CYCLOHEPTENE AS 10,11-DIHYDRO-10,11-EPOXY-5-(3-AMINOPROPYL)-5H-DIBENZO[A,D]CYCLOHEPTENE EXCRETED &.../BOTH/ ACCOUNTED FOR 40% OF DOSE OF PROTRIPTYLINE.

MEAN PLASMA LEVELS FOR PROTRIPTYLINE IN PT ALSO ADMIN NITRAZEPAM INDISTINGUISHABLE FROM PT RECEIVING NO NITRAZEPAM. MEAN PLASMA LEVELS FOR PT RECEIVING SODIUM AMYLOBARBITONE SIGNIFICANTLY DECR. EARLY VALUES MAY BE OF PREDICTIVE IMPORTANCE TO PERMIT EARLY DOSE ADJUSTMENT.