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Desipramine: profile and news
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Jun 14, 2005 Psychopharmacology of Autism Spectrum Disorders Jun 20, 2005 Other information Indication For relief of symptoms in various depressive syndromes, especially endogenous depression. Pharmacology Desipramine, a tertiary amine tricyclic antidepressant, is structurally related to both the skeletal muscle relaxant cyclobenzaprine and the thioxanthene antipsychotics such as thiothixene. Desipramine is used to treat depression, pain of neuropathic origin, attention_deficit hyperactivity disorder, functional enuresis in children, panic and phobic disorder, and to manage some eating disorders. Desipramine inhibits the re-uptake of noradrenaline at the noradrenergic nerve endings and the re-uptake of serotonin (5-hydroxy tryptamine) at the serotoninergic nerve endings in the central nervous system. These two effects are considered to be the likely base of the antidepressant effect of Desipramine. The drug also has a strong anticholinergic effect and serves as an antagonist on a1 and H1 receptors. Mechanism Of Action Desipramine is a tricyclic antidepressant that selectively blocks reuptake of norepinephrine (noradrenaline) from the neural synapse. It also appears to impair serotonin transport. Desipramine also possesses minor anticholinergic activity, through its affinity to muscarinic receptors. Evidence also suggests that Desiprmaine binds to and down regulates histamine and beta adrenergic receptors. Tricyclic drugs are believed to act by restoring normal levels of neurotransmitters by blocking the re-uptake of these substances from the synapse in the central nervous system. Drug Category Antidepressants; Norepinephrine-Reuptake Inhibitors; ATC:N06AA01 Brand Names/Synonyms DMI; Demethylimipramine; Desimipramine; Desimpramine; Desipramin; Desipramine; Desipramine Hcl; Desmethylimipramine; Dezipramine; Dimethylimipramine; Imipramine, Demethyl-; Methylaminopropyliminodibenzyl; Monodemethylimipramine; Norimipramine; Norpramin; Norpramine; Pentofran; Pertofran; Pertofrane; Pertrofane; Sertofran Dosage Forms TABLET Absorption Desipramine hydrochloride is rapidly and almost completely absorbed from the gastrointestinal tract. 90.5% (range 73-92%) of desipramine binds to plasma proteins. Interactions Interactions for Desipramine: 1. 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 traction 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 antiarrhythrnics propatenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, seriraline, 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 T.A. 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 co-therapy, 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. 2. Close supervision and careful adjustment of dosage are required when this drug is given concomitantly with anticholinergic or sympathomimetic drugs. 3. Clinical experience in the concurrent administration of ECT and antidepressant drugs is limited. Thus, if such treatment is essential, the possibility of increased risk relative to benefits should be considered. 4. If desipramine hydrochloride is to be combined with other psychotropic agents such as tranquilizers or sedative/hypnotics, careful consideration should be given to the pharmacology of the agents employed since the sedative effects of desipramine and benzodiazepines (e.g., chlordiazepoxide or diazepam) are additive. Both the sedative and anticholinergic effects of the major tranquilizers are also additive to those of desipramine. 5. Concurrent administration of cimetidine and tricyclic antidepressants can produce clinically significant increases in the plasma levels of the tricyclic antidepressants. Conversely, decreases in plasma levels of the tricyclic antidepressants have been reported upon discontinuation of cimetidine which may result in the loss of the therapeutic efficacy of the tricyclic antidepressant 6. There have been greater than two-fold increases of previously stable plasma levels of tricyclic antidepressants when fluoxetine has been administered in combination with these agents. Chemical IUPAC Name Not Available Chemical Formula C18H22N2 Half Life 21-23 hours Drug Type Approved Drug # Accession No APRD00022 CAS Registry Number 50-47-5 |
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