      Document 0187
 DOCN  DRG0187
 UNIQUE IDENTIFIER        DRG-0060
 NAME OF SUBSTANCE        Imipramine hydrochloride [USAN 1996]
 REGISTRY NUMBER          113-52-0
 RELATED REGISTRY NUMBER  50-49-7 (parent compound)
 STANDARD CHEMICAL NAME   5-[3-(Dimethylamino)propyl]-
                          10,11-dihydro-5-H-dibenz[b,f]azepine
                          monohydrochloride [USAN 1996]
 SYNONYMS                 Antideprin [Merck Index 1989]
 SYNONYMS                 Apo-Imipramine [Merck Index 1983]
 SYNONYMS                 Censtim [Merck Index 1983]
 SYNONYMS                 Censtin [Merck Index 1983]
 SYNONYMS                 Dimipressin [Merck Index 1983]
 SYNONYMS                 DIPD [Merck Index 1983]
 SYNONYMS                 Dyna-Zina [Merck Index 1989]
 SYNONYMS                 Eupramin [Merck Index 1983]
 SYNONYMS                 Imidobenzyle [Merck Index 1983]
 SYNONYMS                 Imizin [Merck Index 1983]
 SYNONYMS                 Imizinum [Merck Index 1983]
 SYNONYMS                 Impril [Merck Index 1983]
 SYNONYMS                 Intalpram [Merck Index 1983]
 SYNONYMS                 Irmin [Merck Index 1983]
 SYNONYMS                 Melipramine [Merck Index 1983]
 SYNONYMS                 Melipramin [Merck Index 1989]
 SYNONYMS                 Novo-pramine [Merck Index 1983]
 SYNONYMS                 Praminil [Merck Index 1983]
 SYNONYMS                 Promiben [Merck Index 1983]
 SYNONYMS                 Surplix [Merck Index 1983]
 SYNONYMS                 Timolet [Merck Index 1983]
 SYNONYMS                 Tipramine [Merck Index 1983]
 SYNONYMS                 5-H-Dibenz[b,f]azepine-5-propanamine,10,11-di-
                          hydro-N,N-dimethyl-,monohydrochloride [USAN
                          1996]
 SYNONYMS                 5-[3-(Dimethylamino)-propyl]-10,11-dihydro-5--
                          H-dibenz[b,f]azepine monohydrochloride [USAN
                          1996]
 SYNONYMS                 Janimine [USAN 1996]
 SYNONYMS                 Tofranil [USAN 1996]
 SYNONYMS                 Imipramine [USAN 1996]
 SYNONYMS                 Berkomine [Merck Index 1989]
 SYNONYMS                 Deprinol [Merck Index 1989]
 SYNONYMS                 Efuranol [Merck Index 1989]
 SYNONYMS                 Imavate [Merck Index 1989]
 SYNONYMS                 Chrytemin [Merck Index 1989]
 SYNONYMS                 Iramil [Merck Index 1989]
 SYNONYMS                 Pryleugan [Merck Index 1989]
 SYNONYMS                 Presamine [Merck Index 1989]
 SYNONYMS                 Feinalmin [Merck Index 1989]
 SYNONYMS                 Imilanyle [Merck Index 1989]
 SYNONYMS                 Iprogen [Merck Index 1989]
 SYNONYMS                 Imiprin [Merck Index 1989]
 SYNONYMS                 Imidol [Merck Index 1989]
 PROTOCOL ID NUMBERS      NIMH 87-DEP
 SECONDARY SOURCE ID      G-22355 [Merck Index 1989]
 SECONDARY SOURCE ID      HSDB 3100 [Merck Index 1989]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: The mechanism of action of
                          the tricyclic antidepressants remains
                          undefined despite the large body of knowledge
                          that has accumulated. Initially the tricyclic
                          antidepressants usually block the reuptake of
                          norepinephrine and serotonin into their
                          respective nerve terminals within the central
                          nervous system. They also block serotonergic,
                          noradrenergic (alpha 1), histaminergic (H1
                          more than H2), and muscarenic receptors to
                          varying degrees. These combined effects on
                          reuptake and receptor occupation reduce the
                          synthesis and turnover of norepinephrine and
                          serotonin and reduce the discharge rates of
                          the neurons of these two transmitters.
                          Correlation of specific neurochemical actions
                          of the tricyclic compounds with their
                          therapeutic effects must take into
                          consideration the one to three weeks that
                          elapse before such effects are apparent.
                          After prolonged administration, blockade of
                          the neuronal reuptake of norepinephrine and
                          serotonin continues and turnover and
                          discharge rates gradually return to normal. A
                          decrease in beta- and alpha2- adrenergic
                          receptor sensitivity and in the number of
                          5HT2 receptors occurs in animals following
                          long term administration of most of the
                          antidepressants and electroconvulsive
                          therapy. Probably no change or a slight
                          increase occurs in the alpha1-adrenergic
                          receptor sensitivity and in the number of
                          muscarinic receptors. All tricyclic compounds
                          are well absorbed orally, extensively
                          metabolized, highly protein bound in plasma
                          and tissue, and eliminated slowly. Mean
                          half-life for imipramine is 7.6 (4 to 17.6)
                          hours. [Drug Evaluations Annual 1992]
                          Mechanism of action is not defintively known.
                          Acts primarily by stimulation of the central
                          nervous system (CNS). Clinical effect is
                          hypothesized as due to potentiation of
                          adrenergic synapses by blocking uptake of
                          norepinephrine at nerve endings. [PDR 1995]
 DISEASES STUDIED/TREATED Treatment of depression [PDR 1995]
 CLASSIFICATION CODE      Antidepressant [PDR 1995]
 OTHER MAJOR USES         For relief of symptoms of depression.
                          Endogenous depression is more likely to be
                          alleviated than other depressive states. May
                          be useful as temporary adjunctive therapy in
                          reducing enuresis in children aged 6 or older
                          [PDR 1995]
 SUBSTANCE INTERACTIONS   Caution should be used when imipramine is
                          given to patients on thyroid medications or
                          receiving methylphenidate hydrochloride.
                          Imipramine may increase CNS depressant
                          effects of alcohol. Concurrent administration
                          of imipramine and elctroshock therapy may
                          increase the hazards. In patients receiving
                          anticholinergic drugs (including
                          antiparkinsonism agents), the atropine-like
                          effects may become more pronounced (e.g.,
                          paralytic ileus). Avoid the concomitant use
                          of decongestants and local anesthetics
                          containing sympathomimetic amines (e.g.,
                          epinephrine, norepinephrine). Use caution
                          when using imipramine with agents that lower
                          blood pressure. Plasma concentration of
                          imipramine may increase when given with
                          hepatic enzymes inhibitors (e.g., cimetidine,
                          fluoxetin). It may decrease when given with
                          hepatic enzyme inducers (e.g., barbiturates,
                          phenytoin). Excessive exposure to sunlight
                          should be avoided since there have been
                          reports of photosensitization. [PDR 1995]
 ADVERSE EFFECTS          May cause orthostatic hypotension,
                          hypertension, tachycardia, palpitation,
                          myocardial infarction, arrhythmias, heart
                          block, electrocardiographic changes,
                          precipitation of congestive heart failure,
                          stroke, hallucinations, disorientation,
                          anxiety, restlessness, agitation, insomnia,
                          hypomania, numbness, tingling, paresthesias
                          of extremities, incoordination, ataxia,
                          tremors, seizures, tinnitus, dry mouth,
                          blurred vision, eye pain, fainting, change in
                          regular heartbeat, nervousness, shakiness,
                          difficult/fast breathing, convulsions, severe
                          drowsiness, fever, vomiting, nausea,
                          diarrhea, trouble in sleeping, vivid dreams,
                          sexual impairment, constipation, abdominal
                          cramps, agranulocytosis, eosinophilia,
                          purpura, thrombocytopenia, skin rash, breast
                          enlargement, jaundice, and altered liver
                          function. [PDR 1995]
 CONTRAINDICATIONS        Contraindicated with the concomitant use of
                          monoamine oxidase inhibiting compounds which
                          may result in hyperpyretic crises or severe
                          convulsive seizures, which can be serious or
                          even fatal. Imipramine hydrochloride is also
                          contraindicated during the acute recovery
                          period after a myocardial infarction and in
                          patients having a known hypersensitivity to
                          the drug. The possibility of
                          cross-sensitivity to other dibenzazepine
                          compounds should be kept in mind. Imipramine
                          should be used with caution in patients who
                          perform potentially hazardous tasks (e.g.,
                          driving or operating machinery). [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Dibenzazepine derivative
                          (tertiary amine) [USP DI 1989]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C19H24N2.HCE [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 316.88 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION: C81.38%; H8.63%;
                          N9.99% (Parent compound) [Merck Index 1983]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Freely soluble in water and in
                          alcohol; soluble in acetone; slightly soluble
                          in ether [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL COMMENT: pKa:9.5 [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: White to off-white,
                          odorless or practically odorless crystalline
                          powder [AHFS Drug Informatio 1995]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 174-175 C [Merck Index 1989]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Tablets, capsules, or solution.
                          [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral or intramuscular
                          administration. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store at 15-30 C (59-86 F) unless
                          otherwise specified by the manufacturer;
                          store in a tight container. [PDR 1995]
 MANUFACTURERS            Ciba
 MANUFACTURERS            Geigy
 MANUFACTURERS            Abbott
 REFERENCES               Rabkin JG, Rabkin R, Harrison W, Wagner G.
                          Effect of imipramine on mood and enumerative
                          measures of immune status in depressed
                          patients with HIV illness. Am J Psychiatry.
                          1994 Apr;151(4):516-23.
 REFERENCES               Wagner GJ, Rabkin JG, Rabkin R. Sexual
                          activity among HIV-seropositive gay men
                          seeking treatment for depression. J Clin
                          Psychiatry. 1993 Dec;54(12):470-5.
 REFERENCES               Nielson BM, Behnke K, Arup P, Christiansen
                          PE, et al. A comparison of fluoxetine and
                          imipramine in the treatment of outpatients
                          with major depressive disorder. Acta
                          Psychiatr Scand. 1993;87(4):269-72.
 REFERENCES               Dening TR, Klimes I, Catalan J, Rizza CR,
                          Peto T. HIV infection, the brain and
                          behaviour: major psychiatric disorder without
                          cognitive impairment before or after the
                          episode. Int J STD AIDS. 1992
                          Mar-Apr;3(2):132-3.
 REFERENCES               Nunes EV, Quitkin FM, Brady R, Stewart JW.
                          Imipramine treatment of methadone maintenance
                          patients with affective disorder and illicit
                          drug use. Am J Psychiatry. 1991
                          May;148(5):667-9.
 REFERENCES               Hintz S, Kuck J, Peterkin JJ, Volk DM, Zisook
                          S. Depression in the context of human
                          immunodeficiency virus infection:
                          implications for treatment. J Clin
                          Psychiatry. 1990 Dec;51(12):497-501.
 REFERENCES               Manning D, Jacobsberg L, Erhart S, Perry S,
                          Frances A. The efficacy of imipramine in the
                          treatment of HIV-related depression. Int Conf
                          AIDS. 1990 Jun 20-23;6(1):141 (abstract no.
                          Th.B.32).
 REFERENCES               Peterkin J, Hintz S, Kuck J, Zisook S.
                          Depression in the context of human
                          immunodeficiency virus infection:
                          implications for treatment. Int Conf AIDS.
                          1990 Jun 20-23;6(3):183 (abstract no.
                          S.B.389).
 REFERENCES               Rabkin JG, Harrison WM. Effect of imipramine
                          on depression and immune status in a sample
                          of men with HIV infection [see comments]. Am
                          J Psychiatry. 1990 Apr;147(4):495-7.
 ENTRY MONTH              8910
 LAST REVISION DATE       951128
 

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