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Imipramine: profile and news
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Jun 14, 2005 Other information Indication For the relief of symptoms of depression and as temporary adjunctive therapy in reducing enuresis in children aged 6 years and older. Pharmacology Imipramine is a tricyclic antidepressant with general pharmacological properties similar to those of structurally related tricyclic antidepressant drugs such as amitriptyline and doxepin. A tertiary amine, imipramine inhibits the reuptake of serotonin more so than most secondary amine tricyclics, meaning that it blocks the reuptake of neurotransmitters serotonin and noradrenaline almost equally. It is also effective in migraine prophylaxis, but not in abortion of acute migraine attack. Mechanism Of Action Imipramine works by inhibiting the re-uptake of the neurotransmitters norepinephrine and serotonin by nerve cells. It binds the Sodium-dependent serotonin transporter and Sodium-dependent noradrenaline transporter, preventing or reducing the reuptake of norepinephrine and serotonin by nerve cells. As norepinephrine and serotonin are used to stimulate the synapse, and depression has been linked to a lack of stimulation of the recipient neuron at a synapse, slowing the reuptake of these neurotransmitters allows them to remain in the synaptic gap longer than it normal, increasing the stimulation of the recipient neuron and relieving the symptoms of depression. However, it does not act primarily by stimulation of the central nervous system. The clinical effect is also hypothesized as being due to potentiation of adrenergic synapses by blocking uptake of norepinephrine at nerve endings. Drug Category Antidepressive Agents, Tricyclic; Norepinephrine-Reuptake Inhibitors; Adrenergic Uptake Inhibitors; ATC:N06AA02; ATC:N06AA03; ATC:N06AA06 Brand Names/Synonyms Antideprin; Apo-Imipramine; Berkomine; Censtim; Censtin; DPID; Declomipramine; Dimipressin; Dyna-Zina; Dynaprin; Estraldine; Eupramin; G-22355; IM; Imavate; Imidobenzyle; Imipramina; Imipramine; Imipramine Hcl; Imiprin; Imizin; Imizine; Imizinum; Impramine; Impril; Intalpram; Iramil; Irmin; Janimine; Melipramin; Melipramine; Nelipramin; Norfranil; Novopramine; Pramine; Prazepine; Presamine; Promiben; Psychoforin; Sk-Pramine; Surmontil; Surplix; Timolet; Tipramine; Tofranil; Tofranil, Base; Tofranil-Pm; Tofraniln A; Trimipramine Maleate Dosage Forms TABLET Absorption Rapidly and well absorbed after oral administration Interactions -->Interactions for Imipramine: In occasional susceptible patients or in those receiving anticholinergic drugs (including antiparkinsonism agents) in addition, the atropine-like effects may become more pronounced (e.g., paralytic ileus). Close supervision and careful adjustment of dosage is required when this drug is administered concomitantly with anticholinergic drugs. Avoid the use of preparations such as decongestants and local anesthetics which contain any sympathomimetic amine (e.g., epinephrine, norepinephrine), since it has been reported that tricyclic antidepressants can potentiate the effects of catecholamines. Caution should be exercised when imipramine hydrochloride is used with agents that lower blood pressure. Imipramine hydrochloride may potentiate the effects of CNS depressant drugs. The plasma concentration of imipramine may increase when the drug is given concomitantly with hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decrease by concomitant administration of hepatic enzyme inducers (e.g., barbiturates, phenytoin), and adjustment of the dosage of imipramine may therefore be necessary. Drugs Metabolized by P450 2D6 The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7 to 10% of caucasians are so called "poor metabolizers"); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8-fold increase in plasma AUC of the TCA). In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble p.o. metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e. g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition, and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCA5 with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from cotherapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6. Chemical IUPAC Name Not Available Chemical Formula C19H24N2 Half Life 11–25 hours Drug Type Approved Drug # Accession No APRD00672 CAS Registry Number 50-49-7 |
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