Imipramine

Imipramine

Clinical data
Trade names	Tofranil, others
AHFS/Drugs.com	Monograph
MedlinePlus	a682389
Pregnancy category	AU: C US: N (Not classified yet)
Routes of administration	Oral
ATC code	N06AA02 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) CA: ℞-only UK: POM (Prescription only) US: ℞-only
Pharmacokinetic data
Bioavailability	94-96%
Protein binding	86%
Metabolism	Hepatic (CYP1A2, CYP2C19, CYP2D6) Main active metabolite desipramine
Biological half-life	20 hours
Excretion	Renal (80%), Faecal (20%) (mostly as inactive metabolites)
Identifiers
IUPAC name 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N,N-dimethylpropan-1-amine
Synonyms	G 22355
CAS Number	50-49-7 Y
PubChem (CID)	3696
IUPHAR/BPS	357
DrugBank	DB00458 Y
ChemSpider	3568 Y
UNII	OGG85SX4E4 Y
KEGG	D08070 Y
ChEBI	CHEBI:47499 Y
ChEMBL	CHEMBL11 Y
ECHA InfoCard	100.000.039
Chemical and physical data
Formula	C19H24N2
Molar mass	280.407 g/mol
3D model (Jmol)	Interactive image
SMILES c1cc3c(cc1)CCc2c(cccc2)N3CCCN(C)C
InChI InChI=1S/C19H24N2/c1-20(2)14-7-15-21-18-10-5-3-8-16(18)12-13-17-9-4-6-11-19(17)21/h3-6,8-11H,7,12-15H2,1-2H3 Y Key:BCGWQEUPMDMJNV-UHFFFAOYSA-N Y

Imipramine, sold as Tofranil and also known as melipramine, is a tricyclic antidepressant (TCA) of the dibenzazepine group. Imipramine is mainly used in the treatment of major depression and enuresis (inability to control urination).

Imipramine was discovered in 1951. It has also been evaluated for use in panic disorder.

Imipramine is used in the treatment of depression, such as depression associated with agitation or anxiety. It is similar in efficacy to the antidepressant drug moclobemide. It has also been used to treat nocturnal enuresis because of its ability to shorten the time of delta wave stage sleep, where wetting occurs. In veterinary medicine, imipramine is used with xylazine to induce pharmacologic ejaculation in stallions.

Those listed in Italic text below denote common side effects.

Imipramine, a tertiary amine, affects numerous neurotransmitter systems known to be involved in the etiology of depression, anxiety, ADHD, enuresis and numerous other mental and physical conditions. Imipramine is similar in structure to some muscle relaxants, and has a significant analgesic effect and, thus, is very useful in some pain conditions.

The mechanisms of imipramine's medicinal action include, but are not limited to, effects on:

Within the body, imipramine is converted to desipramine, another TCA.

In the late 1950s, imipramine was the first tricyclic antidepressant to be developed (by Ciba). At the first international congress of neuro-pharmacology in Rome, September 1958 Dr Freyhan from the University of Pennsylvania discussed as one of the first clinicians the effects of imipramine in a group of 46 patients, most of them diagnosed as "depressive psychosis". The patients were selected for this study based on symptoms such as depressive apathy, kinetic retardation and feelings of hopelessness and despair. In 30% of all patients, he reported optimal results, and in around 20%, failure. The side effects noted were atropine-like, and most patients suffered from dizziness. Imipramine was first tried against psychotic disorders such as schizophrenia, but proved insufficient. As an antidepressant, it did well in clinical studies and it is known to work well in even the most severe cases of depression. It is not surprising, therefore, that imipramine may cause a high rate of manic and hypomanic reactions in hospitalized patients with pre-existing bipolar disorder, with one study showing that up to 25% of such patients maintained on Imipramine switched into mania or hypomania. Such powerful antidepressant properties have made it favorable in the treatment of treatment-resistant depression.