Protriptyline

263.384

263.38

207-119-9

4NDU154T12

DTXSID0023535

N - Nervous system

2921499090

12

4.7

Solid

1.026 g/cm3

169 - 171 °C (protriptyline hydrochloride)

163-164 °C @ Press: 0.35 Torr

198.3ºC

2.31e-04 g/L

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]

ODORLESS OR HAS NOT MORE THAN SLIGHT ODOR & HAS BITTER TASTE; WHITE TO YELLOWISH POWDER /HYDROCHLORIDE/

REASONABLY STABLE IN LIGHT, STABLE IN AIR, & STABLE IN HEAT UNDER USUAL PREVAILING TEMP /HYDROCHLORIDE/

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

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.

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.

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.

LD50 Rat oral 240 mg/kg|LD50 Rat ip 42 mg/kg|LD50 Mouse oral 269 mg/kg|LD50 Mouse ip 67 mg/kg|For more Non-Human Toxicity Values (Complete) data for PROTRIPTYLINE (8 total), please visit the HSDB record page.

For the treatment of depression.

Protriptyline is a tricyclic antidepressant that was previously widely used in the therapy of major depression. Most of the tricyclic antidepressants have been shown to cause a low rate of mild and transient serum enzyme elevations and rare cases of clinically apparent acute cholestatic liver injury. The potential hepatotoxicity specifically of protriptyline, however, has not been well defined.

Antidepressant Agents

Adrenergic Uptake Inhibitors; Antidepressive Agents, Tricyclic|TRICYCLIC (DIBENZOCYCLOHEPTENE) ANTIDEPRESSANT DRUG USEFUL IN MGMNT OF ENDOGENOUS & EXOGENOUS DEPRESSIONS. IT ALSO INCR PSYCHOMOTOR ACTIVITY; THIS PROPERTY ENHANCES ITS USE IN WITHDRAWN & ANERGIC PT. /HYDROCHLORIDE/|...MAY BE PARTICULARLY USEFUL IN TREATING DEPRESSED PT WHOSE PREDOMINANT MANIFESTATIONS OF ILLNESS ARE PSYCHOMOTOR RETARDATION, APATHY, & FATIGUE... /HYDROCHLORIDE/|...BECAUSE OF THEIR SEDATIVE PROPERTY. ...MAY BE USEFUL IN INITIAL THERAPY OF DEPRESSED PT WITH SLEEP LOSS... DRUGS DO DECR NUMBER OF AWAKENINGS, INCR STAGE-4 SLEEP, & MARKEDLY DECR REM TIME. /TRICYCLIC ANTIDEPRESSANTS/|For more Therapeutic Uses (Complete) data for PROTRIPTYLINE (8 total), please visit the HSDB record page.

...POSSESSES ANTICHOLINERGIC PROPERTIES &, HENCE, SHOULD NOT BE USED IN PT WITH PYLORIC OBSTRUCTION, GLAUCOMA, OR URINARY RETENTION. /HYDROCHLORIDE/|...THOSE WITH SYMPTOMS OF AGITATION, ANXIETY, & TENSION FREQUENTLY BECOME MORE DISTURBED WITH USE OF PROTRIPTYLINE.|DRUG MAY AGGRAVATE ANXIETY, & IT SHOULD NOT BE USED IN ANXIOUS DEPRESSED PT UNLESS IT IS GIVEN WITH SEDATIVE DRUG, SUCH AS PHENOTHIAZINE WITH SEDATIVE EFFECTS...OR MORE CONVENTIONAL SEDATIVE DRUG... /HYDROCHLORIDE/|TACHYCARDIA & POSTURAL HYPOTENSION OCCUR MORE FREQUENTLY...THAN WITH OTHER ANTIDEPRESSANT DRUGS; HENCE, PT WITH CARDIOVASCULAR DISORDERS & ELDERLY PT SHOULD BE OBSERVED CLOSELY FOR THESE UNTOWARD EFFECTS. /HYDROCHLORIDE/|For more Drug Warnings (Complete) data for PROTRIPTYLINE (28 total), please visit the HSDB record page.

5. 5= EXTREMELY TOXIC: PROBABLE ORAL LETHAL DOSE (HUMAN) 5-50 MG/KG, BETWEEN 7 DROPS & 1 TEASPOONFUL FOR 70 KG PERSON (150 LB). /HYDROCHLORIDE/

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. The effectiveness of antidepressants appear after approximately two weeks following recommended adminsitration schedule. Gradual changes are thought to occur in the cerebral cortex and hippocampus, involved in emotion regulation as part of the limbic system, as receptor sensitivity is enhanced. While α₁ and β₁ receptors are sensitized, α₂ receptors are desensitized (leading to increased noradrenaline production). Tricyclics are also reported to alter the perceptions of pain, including neuropathic or neuralgic pain, so they may exhibit analgesic properties. The mechanism of action behind this analgesic property is not fully understood; however, it is thought to involve modulation of endogenous opioid systems in the CNS via an indirect serotonergic route. Tricyclic antidepressants are also effective in relieving migraine prophylaxis, but not in abortion of acute migraine attack, potentially via their serotonergic effects.

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. (See all compounds classified as Antidepressive Agents, Tricyclic.)|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. (See all compounds classified as Adrenergic Uptake Inhibitors.)

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.

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.

AFTER A SINGLE ORAL DOSE OF 30 MG TO 8 SUBJECTS, PEAK LEVELS RANGED FROM 10.4-22.3 NG/ML, 6-12 HR AFTER ADMIN. MEAN T/2 WAS 74.3 HR & RANGED FROM 53.6-91.7 HR IN INDIVIDUAL SUBJECTS.|SINGLE ORAL DOSE OF HCL-SALT ADMIN TO 8 PERSONS. EST 1ST PASS METAB WAS RELATIVELY SMALL, 10-25% OF DOSE, ASSUMING COMPLETE ABSORPTION. MEAN VOL OF DISTRIBUTION 22.5 L/KG & RANGED FROM 15.0-31.2 L/KG. CONCLUSION WAS THAT LONG T/2 IS CORRELATED WITH SMALL 1ST PASS METABOLISM.|PLASMA LEVELS IN 30 PT. AFTER 3.5 WK TREATMENT @ 40 MG/DAY, PLASMA LEVELS RANGED FROM 430-1430 NMOL/L. SINGLE DOSE STUDIES IN 5 VOLUNTEERS SUGGEST THAT VOL OF DISTRIBUTION OF PROTRIPTYLINE SHOWS LITTLE INTERSUBJECT VARIATION. HOWEVER, T/2 MAY VARY, RANGING FROM 54-198 HR.

Protriptyline acts by decreasing the reuptake of norepinephrine and serotonin (5-HT).|ACTION OF TRICYCLIC ANTIDEPRESSANTS ON METAB OF CATECHOLAMINES & INDOLEAMINES IN BRAIN HAS CONTRIBUTED SIGNIFICANTLY TO "BIOGENIC AMINE HYPOTHESIS" OF DEPRESSION. ... /ALL/ BLOCK RE-UPTAKE OF NOREPINEPHRINE BY ADRENERGIC NERVE TERMINALS. /DEMETHYLATED ANALOGS ARE MORE POTENT IN THIS ACTION/ /TRICYCLIC ANTIDEPRESSANTS/

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.

Hydrochloride, Protriptyline

AVAILABLE IN 5 & 10 MG TABLETS /HYDROCHLORIDE/

...MAY BE EXTRACTED FROM ALKALINIZED SAMPLE BY ORGANIC SOLVENT. REEXTRACTED INTO DILUTE ACID YIELDS SOLN WHOSE PORTRIPTYLINE CONTENT CAN BE ASSAYED BY SPECTROFLUOROMETRY.

GAS CHROMATOGRAPHY METHOD USING EITHER A CONVENTIONAL PACKED COLUMN OR A CAPILLARY COLUMN FOR MEASUREMENT OF THERAPEUTIC PLASMA CONCN OF TRICYCLIC ANTIDEPRESSANT DRUGS & THEIR DEMETHYLATED METABOLITES.|HIGH PRESSURE LIQUID CHROMATOGRAPHIC PROCEDURES REPORTED FOR DETERMINATION OF AMITRIPTYLINE & NORTRIPTYLINE. SEPARATIONS & QUANTITATIONS WERE CARRIED OUT @ AMBIENT TEMP USING A SILICA COLUMN WITH A VARIABLE WAVELENGTH UV DETECTOR. ANALYSIS PERFORMED ON 0.25 ML SERUM.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals