Definition
Description
Top Gene Interactions
Related Pathways
General Information
- Metabolism: Desipramine is extensively metabolized in the liver by CYP2D6 (major) and CYP1A2 (minor) to 2-hydroxydesipramine, an active metabolite. 2-hydroxydesipramine is thought to retain some amine reuptake inhibition and may possess cardiac depressant activity. The 2-hydroxylation metabolic pathway of desipramine is under genetic control. Route of Elimination: Desipramine is metabolized in the liver, and approximately 70% is excreted in the urine. Half Life: 7-60+ hours; 70% eliminated renally
- Uses/Sources: For relief of symptoms in various depressive syndromes, especially endogenous depression. It has also been used to manage chronic peripheral neuropathic pain, as a second line agent for the management of anxiety disorders (e.g. panic disorder, generalized anxiety disorder), and as a second or third line agent in the ADHD management.
- Treatment: Obtain an ECG and immediately initiate cardiac monitoring. Protect the patient's airway, establish an intravenous line, and initiate gastric decontamination. A minimum of 6 hours of observation with cardiac monitoring and observation for signs of CNS or respiratory depression, hypotension, cardiac dysrhythmias and/or conduction blocks, and seizures is necessary. If signs of toxicity occur at any time during this period, extended monitoring is required. Follow ECG, renal function, CPK, and arterial blood gasses as clinically indicated. (L1712)
- Route of Exposure: Desipramine hydrochloride is rapidly and almost completely absorbed from the gastrointestinal tract. It undergoes extensive first-pass metabolism. Peak plasma concentrations are attained 4 - 6 hours following oral administration.
Toxicity
- Carcinogenicity: No indication of carcinogenicity to humans (not listed by IARC).
- Toxicity: LD50: 290 mg/kg (Mouse) (A308) LD50: 320 mg/kg (Rat) (A308)
Mechanism of Action
Target Name | Mechanism of Action | References |
---|---|---|
Serum albumin Potassium voltage-gated channel subfamily H member 2 Muscarinic acetylcholine receptor M3 Muscarinic acetylcholine receptor M4 Muscarinic acetylcholine receptor M5 5-hydroxytryptamine receptor 2A 5-hydroxytryptamine receptor 2C 5-hydroxytryptamine receptor 1A Alpha-2A adrenergic receptor Sodium-dependent dopamine transporter D(2) dopamine receptor D(1A) dopamine receptor Histamine H2 receptor Solute carrier family 22 member 1 Alpha-1 adrenergic receptor Histamine H3 receptor Alpha-2 adrenergic receptor |
12431845 9537821 18448342 9686407 8100134 10447960 20945906 17846138 9400006 15911273 12873512 11266163 18348514 17690258 7855217 8876023 10425082 18788725 |
|
Muscarinic acetylcholine receptor M1 Muscarinic acetylcholine receptor M2 Sodium-dependent serotonin transporter Sodium-dependent noradrenaline transporter Histamine H1 receptor Beta-1 adrenergic receptor Beta-2 adrenergic receptor Sphingomyelin phosphodiesterase |
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. |
21916421 16989524 19791802 8741184 10411589 17558518 17846138 17417877 9400006 9422361 16300628 12837768 12431845 8730743 15093822 7816863 8100134 15814154 20945906 17139284 20378347 23385211 14689449 12464448 16803890 6146381 19632110 12393876 19836247 16675639 10467920 15705795 19722525 18951020 17016423 20462211 19713106 8988485 15002740 7855217 17123820 14960314 18557608 9537821 18771916 12137927 20131864 10424850 11752352 16140280 7945993 17690258 19329313 |
Desipramine Interacts with Diseases
Disease | Inference Score | References/Inference Genes |
Brain Ischemia | 22.25 |
|
Cocaine dependence | 20.04 |
|
Trigeminal Neuralgia | 19.97 |
|
Alzheimer's Disease | 18.64 |
|
Radiation Injuries, Experimental | 16.74 |
|
Alcoholic liver cirrhosis | 15.73 |
|
Schizophrenia | 15.5 |
|
Cardiomyopathies | 15.06 |
|
Prostatic Neoplasms | 14.7 |
|
Reperfusion Injury | 14.7 |
|
HIV Wasting Syndrome | 14.26 |
|
Heat Stroke | 14.01 |
|
Lung Neoplasms | 13.73 |
|
Hyperalgesia | 13.46 |
|
Stomach Neoplasms | 12.55 |
|
Neoplasm Invasiveness | 12.29 |
|
Nervous System Diseases | 11.59 |
|
Mitochondrial Myopathies | 11.2 |
|
Pleurisy | 11.07 |
|
Pulmonary Fibrosis | 10.9 |
|