Product InformationRegistration Status: Active
APO-IMIPRAMINE TABLET 10mg is approved to be sold in Singapore with effective from 1990-04-20. It is marketed by PHARMAFORTE SINGAPORE PTE LTD, with the registration number of SIN04155P.
This product contains Imipramine 10mg in the form of TABLET, FILM-COATED. It is approved for ORAL use.
This product is manufactured by APOTEX INC in CANADA.
It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.
Imipramine, the prototypical tricyclic antidepressant (TCA), is a dibenzazepine-derivative TCA. TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, imipramine does not affect mood or arousal, but may cause sedation. In depressed individuals, imipramine exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Tertiary amine TCAs, such as imipramine and amitriptyline, are more potent inhibitors of serotonin reuptake than secondary amine TCAs, such as nortriptyline and desipramine. TCAs also block histamine H1 receptors, α1-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively [A6584]. Imipramine has less sedative and anticholinergic effects than the tertiary amine TCAs, amitriptyline and clomipramine. Imipramine may be used to treat depression and nocturnal enuresis in children [FDA Label]. Unlabeled indications include chronic and neuropathic pain (including diabetic neuropathy), panic disorder, attention-deficit/hyperactivity disorder (ADHD), and post-traumatic stress disorder (PTSD) [L1349,L1348,A31900,L1351,L1352,L1353,A31904].
For the relief of symptoms of depression and as temporary adjunctive therapy in reducing enuresis in children aged 6 years and older [FDA Label]. May also be used off-label to manage panic disorders with or without agoraphobia, as a second line agent for ADHD in children and adolescents, to manage bulimia nervosa, for short-term management of acute depressive episodes in bipolar disorder and schizophrenia, for the treatment of acute stress disorder and posttraumatic stress disorder, and for symptomatic treatment of postherpetic neuralgia and painful diabetic neuropathy [L1349,L1348,A31900,L1351,L1352,L1353,A31904].
Mechanism of Action
Imipramine works by inhibiting the neuronal reuptake of the neurotransmitters norepinephrine and serotonin [A6584,T116]. It binds the sodium-dependent serotonin transporter and sodium-dependent norepinephrine transporter reducing the reuptake of norepinephrine and serotonin by neurons. Depression has been linked to a lack of stimulation of the post-synaptic neuron by norepinephrine and serotonin [A31933]. Slowing the reuptake of these neurotransmitters increases their concentration in the synaptic cleft, producing knock-on effects in protein kinase signalling which is thought to contribute to changes in neurotransmission and brain physiology which relieves symptoms of depression [A31939].
- Rapidly and well absorbed (>95%) after oral administration [A31907]. The primary site of absorption is the small intestine as the basic amine groups are ionized in the acidic environment of the stomach, preventing movement across tissues. Bioavailability ranges from 29-77% due to high inter-individual variability. Peak plasma concentration is usually attained 2-6 hours following oral administration. Absorption is unaffected by food.
- Imipramine has a high apparent volume of distribution of 10-20 L/kg [A31907]. The drug is known to accumulate in the brain at concentrations 30-40 times that in systemic circulation.
- Imipramine is nearly exclusively metabolized by the liver [A31907]. Imipramine is converted to desipramine by CYP1A2, CYP3A4, CYP2C19. Both imipramine and desipramine are hydroxylated by CYP2D6 [A31915]. Desipramine is an active metabolite. Minor metabolic pathways include dealkylation to form an imidodibenzyl product as well as demethylation of desipramine to didemethylimipramine and subsequent hydroxylation [A31907]. Less than 5% of orally administered imipramine is excreted unchanged.
Imipramine has a mean clearance of 1 L/h/kg. Its active metabolite, desipramine has a mean clearance of 1.8 L/h/kg [A31907].
The anticholinergic actvity of imipramine can produce dry mucous membranes, blurred vision, increased intraocular pressure, hyperthermia, constipation, adynamic ileus, urinary retention, delayed micturition, and dilation of the urinary tract [L1360]. Central nervous system and neuromuscular effects include drowsiness, lethargy, fatigue, agitation, excitement, nightmares, restlessness, insomnia, confusion, disturbed concentration, disorientation, delusions, and hallucinations. Effects on the GI tract include anorexia, nausea and vomiting, diarrhea, abdominal cramps, increases in pancreatic enzymes, epigastric distress, stomatitis, peculiar taste, and black tongue. Rarely agranulocytosis, thrombocytopenia, eosinophilia, leukopenia, and purpura have occured. Infants whose mothers were receiving tricyclic antidepressants prior to delivery have experienced cardiac problems, irritability, respiratory distress, muscle spasms, seizures, and urinary retention. Serotonin syndrome can occur when used in conjunction with other pro-serotonergic drugs. ### LD50 Values Rat - Oral 250 mg/kg - Intraperitoneal 79mg/kg - Subcutaneous 250 mg/kg - Intravenous 15.9 mg/kg Mouse - Oral 188 mg/kg - Intraperitoneal 51.6 mg/kg - Subcutaneous 195 μg/kg - Intravenous 21 mg/kg Human range of toxicity is considered to include single dosages greater than 5 mg/kg.
10,11-dihydro-N,N-Dimethyl-5H-dibenz[b,F]azepine-5-propanamine | 3-(5H-DIBENZO[b,F]azepin-5-yl)-N,N-dimethylpropan-1-amine | 5-[3-(dimethylamino)Propyl]-10,11-dihydro-5H-dibenz[b,F]azepine | Antideprin | Imipramin | Imipramine | Imipraminum | Imizine | Irmin | Melipramine | N-(gamma-Dimethylaminopropyl)iminodibenzyl | N-(γ-dimethylaminopropyl)iminodibenzyl | Imipramine |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.