      Document 0078
 DOCN  DRG0078
 UNIQUE IDENTIFIER        DRG-0169
 NAME OF SUBSTANCE        Amitriptyline hydrochloride [USAN 1996]
 REGISTRY NUMBER          549-18-8
 RELATED REGISTRY NUMBER  50-48-6
 RELATED REGISTRY NUMBER  8058-15-9
 STANDARD CHEMICAL NAME   1-Propanamine,
                          3-(10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5-
                          -ylidene) -N,N-dimethyl-, hydrochloride [USAN
                          1996]
 SYNONYMS                 Amitid [USAN 1996]
 SYNONYMS                 Amitril [USAN 1996]
 SYNONYMS                 Elavil [USAN 1996]
 SYNONYMS                 Endep [USAN 1996]
 SYNONYMS                 Deprex [Merck Index 1989]
 SYNONYMS                 Domical [Merck Index 1989]
 SYNONYMS                 Euplit [Merck Index 1989]
 SYNONYMS                 Lentizol [Merck Index 1989]
 SYNONYMS                 Miketorin [Merck Index 1989]
 SYNONYMS                 Saroten [Merck Index 1989]
 SYNONYMS                 Sylvemid [Merck Index 1989]
 SYNONYMS                 Tryptizol [Merck Index 1989]
 PROTOCOL ID NUMBERS      NIAID CPCRA 022
 PROTOCOL ID NUMBERS      NIAID ACTG 242
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Inhibits the membrane pump
                          mechanism responsible for uptake of
                          norepinephrine and serotonin in adrenergic
                          and serotonergic neurons. Pharmacologically,
                          this action may potentiate or prolong
                          neuronal activity since reabsorption of these
                          biogenic amines is important physiologically
                          in terminating transmitting activity. Since
                          norepinephrine and serotonin can carry pain
                          messages to the brain from other parts of the
                          body, reducing the reabsorption of these
                          substances can potentially decrease the pain
                          felt by a person. Amitriptyline is rapidly
                          absorbed and metabolized by N-demethylation
                          and bridge hydroxylation. Peak plasma
                          concentrations occur within 2-12 h after oral
                          or IM therapy. The plasma half-life ranges
                          from 10-50 h. About 25-50% of a dose is
                          excreted in urine as inactive metabolites
                          within 24 h. [PDR 1995] [NIAID CPCRA 022]
                          [AHFS Drug Information 1995]
 DISEASES STUDIED/TREATED Relief or reduction of pain caused by
                          HIV-associated peripheral neuropathy [NIAID
                          CPCRA 022]
 CLASSIFICATION CODE      Antidepressant [USAN 1996]
 CLASSIFICATION CODE      Analgesic (NIAID ACTG 242)
 OTHER MAJOR USES         Relief of symptoms of depression; relief of
                          neuropathic pain in various peripheral
                          neuropathies [NIAID CPCRA 022] [PDR 1995]
 SUBSTANCE INTERACTIONS   Interacts with monoamine oxidase inhibitors,
                          cimetidine, ethchlorvynol, and
                          sympathomimetic and anticholinergic agents.
                          May block the antihypertensive action of
                          guanethidine or similarly acting compounds.
                          May potentiate the effects of alcohol,
                          barbiturates, and other CNS depressants. [PDR
                          1995] [AHFS Drug Information 1995]
 ADVERSE EFFECTS          Adverse effects may include sedation,
                          orthostatic hypotension, tachycardia,
                          arrhythmias, prolongation of conduction time,
                          myocardial infarction, stroke, coma,
                          seizures, hallucinations, paralytic ileus,
                          hyperpyrexia, urinary retention, skin rash,
                          bone marrow depression, dry mouth, blurred
                          vision, and elevated or decreased blood sugar
                          levels. [NIAID CPCRA 022] [PDR 1995]
 CONTRAINDICATIONS        Contraindicated in patients with prior
                          hypersensitivity to the drug and those in the
                          acute recovery phase following myocardial
                          infarction. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Dibenzocycloheptadiene
                          derivative [PDR 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 313.87 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C2OH23NHCl [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 196-197 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Freely soluble in water,
                          chloroform, and alcohol [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL COMMENT: pKa 9.4 [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: White, odorless
                          crystals [PDR 1995] [Merck Index 1989]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: 10, 25, 50, 75, 100, and 150 mg
                          tablets; 10 mg/ml solution vials. [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral; intramuscular
                          injection. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store at or below 30 C (86 F).
                          Protect tablets from light. Protect solution
                          from freezing. [PDR 1995]
 MANUFACTURERS            University of Iowa
 REFERENCES               Shepherd J, Shepherd C, Tonozzi C, Boysen E.
                          Severe co-trimoxazole reaction in a man with
                          AIDS. J Am Board Fam Pract. 1995
                          Mar-Apr;8(2):130-3.
 REFERENCES               Holsboer F, Grasser A, Friess E, Wiedemann K.
                          Steroid effects on central neurons and
                          implications for psychiatric and neurological
                          disorders. Ann N Y Acad Sci. 1994 Nov
                          30;746:345-59.; discussion 359-61.
 REFERENCES               Benoliel R, Eliav E, Elishoov H, Sharav Y.
                          Diagnosis and treatment of persistent pain
                          after trauma to the head and neck. J Oral
                          Maxillofac Surg. 1994 Nov;52(11):1138-47;
                          discussion 1147-8.
 REFERENCES               Jones ME, Brettle RP, Busuttil A, Inglis MH,
                          Bell JE, Willocks L. Sudden death in
                          HIV-infected drug users. Presumptive overdose
                          in an HIV-positive narcotic addict. J Infect.
                          1993 Jul;27(10:79-81.
 REFERENCES               McQuay HJ, Carroll D, Glynn CJ. Dose-response
                          for analgesic effect of amitriptyline in
                          chronic pain. Anaesthesia. 1993
                          Apr;48(4):281-5.
 REFERENCES               Kerrick JM, Fine PG, Lipman AG, Love G.
                          Low-dose amitriptyline as an adjunct to
                          opioids for postoperative orthopedic pain: a
                          placebo-controlled trial. Pain. 1993
                          Mar;52(3):325-30.
 REFERENCES               Max MB, Lynch SA, Muir J, Shoaf SE, Smoller
                          B, Dubner R. Effects of desipramine,
                          amitriptyline, and fluoxetine on pain in
                          diabetic neuropathy [see comments]. N Engl J
                          Med. 1992 May 7;326(19):1250-6.
 REFERENCES               Watson CP, Chipman M, Reed K, Evans RH,
                          Birkett N. Amitriptyline versus maprotiline
                          in postherpetic neuralgia: a randomized,
                          double-blind, crossover trial. Pain. 1992
                          Jan;48(1):29-36.
 REFERENCES               Bowsher D. Acute herpes zoster and
                          postherpetic neuralgia: effects of acyclovir
                          and outcome of treatment with amitriptyline
                          [see comments]. Br J Gen Pract. 1992
                          Jun;42(359):244-6.
 REFERENCES               McQuay HJ, Carroll D, Glynn CJ. Low dose
                          amitriptyline in the treatment of chronic
                          pain. Anaesthesia. 1992 Aug;47(8):646-52.
 ENTRY MONTH              9305
 LAST REVISION DATE       960403
 

SOURCE: National Library of Medicine, Bethesda, MD.  Distributed by AEGIS.
