Desipramine, sold under the brand name Norpramin among others, is a

tricyclic antidepressant Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants, which is important for the management of depression. They are second-line drugs next to SSRIs. TCAs were discovered in the early 1950s and wer ...

(TCA) used in the treatment of depression. It acts as a relatively selective

norepinephrine reuptake inhibitor A norepinephrine reuptake inhibitor (NRI, NERI) or noradrenaline reuptake inhibitor or adrenergic reuptake inhibitor (ARI), is a type of drug that acts as a reuptake inhibitor for the neurotransmitters norepinephrine (noradrenaline) and ep ...

, though it does also have other activities such as weak

serotonin reuptake inhibitor A serotonin reuptake inhibitor (SRI) is a type of drug which acts as a reuptake inhibitor of the neurotransmitter serotonin (5-hydroxytryptamine, or 5-HT) by blocking the action of the serotonin transporter (SERT). This in turn leads to incre ...

y, α₁-blocking,

antihistamine Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provide ...

, and

anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system. These agents inhibit the parasympathetic nervous sys ...

effects. The drug is not considered a first-line treatment for depression since the introduction of

selective serotonin reuptake inhibitor Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs increase the extracellul ...

(SSRI)

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common Side effect, side-effects of antidepressants include Xerostomia, dry mouth, weig ...

s, which have fewer

side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

s and are safer in

overdose A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended.

Medical uses

Desipramine is primarily used for the treatment of depression. It may also be useful to treat symptoms of

attention-deficit hyperactivity disorder Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inappr ...

(ADHD). Evidence of benefit is only in the short term, and with concerns of side effects its overall usefulness is not clear. Desipramine at very low doses is also used to help reduce the pain associated with functional dyspepsia. It has also been tried, albeit with little evidence of effectiveness, in the treatment of cocaine dependence. Evidence for usefulness in

neuropathic pain Neuropathic pain is pain caused by damage or disease affecting the somatosensory system. Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli (allodynia). It may have continuous ...

is also poor.

Side effects

Desipramine tends to be less

sedating Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Examples of drugs which can be used for sedation include isoflurane, diethyl ether, ...

than other TCAs and tends to produce fewer

effects such as dry mouth,

constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel moveme ...

urinary retention Urinary retention is an inability to completely empty the bladder. Onset can be sudden or gradual. When of sudden onset, symptoms include an inability to urinate and lower abdominal pain. When of gradual onset, symptoms may include loss of bladd ...

blurred vision Blurred vision is an ocular symptom where vision becomes less precise and there is added difficulty to resolve fine details. Temporary blurred vision may involve dry eyes, eye infections, alcohol poisoning, hypoglycemia, or low blood pressure ...

, and

cognitive Cognition refers to "the mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception, attention, thought ...

or memory impairments.

Overdose

Desipramine is particularly toxic in cases of overdose, compared to other antidepressants. Any overdose or suspected overdose of desipramine is considered to be a medical emergency and can result in death without prompt medical intervention.

Pharmacology

Pharmacodynamics

Desipramine is a very potent and relatively selective

(NRI), which is thought to enhance

noradrenergic Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...

neurotransmission Neurotransmission (Latin: ''transmissio'' "passage, crossing" from ''transmittere'' "send, let through") is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron (the presynaptic neuron), ...

. Based on one study, it has the highest affinity for the norepinephrine transporter (NET) of any other TCA, and is said to be the most noradrenergic and the most selective for the NET of the TCAs. The observed effectiveness of desipramine in the treatment of ADHD was the basis for the development of the selective NRI

atomoxetine Atomoxetine, sold under the brand name Strattera, among others, is a medication used to treat attention deficit hyperactivity disorder (ADHD). It may be used alone or along with psychostimulants. It is also used as a cognitive enhancer to imp ...

and its use in ADHD. Desipramine has the weakest

and

effects of the TCAs. It tends to be slightly activating/stimulating rather than

, unlike most others TCAs. Whereas other TCAs are useful for treating

insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...

, desipramine can cause insomnia as a side effect due to its activating properties. The drug is also not associated with

weight gain Weight gain is an increase in body weight. This can involve an increase in muscle mass, fat deposits, excess fluids such as water or other factors. Weight gain can be a symptom of a serious medical condition. Description Weight gain occurs w ...

, in contrast to many other TCAs. Secondary amine TCAs like desipramine and

nortriptyline Nortriptyline, sold under the brand name Pamelor, among others, is a medication used to treat depression. This medicine is used for: neuropathic pain, attention deficit hyperactivity disorder (ADHD), smoking cessation and anxiety. As with many ...

have a lower risk of

orthostatic hypotension Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a person's blood pressure drops when standing up or sitting down. Primary orthostatic hypertension is also often referred to as neurogenic orthostatic hyp ...

than other TCAs, although desipramine can still cause moderate orthostatic hypotension.

Pharmacokinetics

Desipramine is the major

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, ...

of imipramine and lofepramine.

Chemistry

Desipramine is a

tricyclic compound Tricyclics are chemical compounds that contain three interconnected rings of atoms. Many compounds have a tricyclic structure, but in pharmacology, the term has traditionally been reserved to describe heterocyclic drugs. Among these are antid ...

, specifically a

dibenzazepine Dibenzazepine (iminostilbene) is a chemical compound with two benzene functional group, rings fused to an azepine functional group, group. See also * Benzazepine * Dibenzothiazepine * Dibenzothiepin * Dibenzoxepin References External links ...

, and possesses three rings fused together with a

side chain In organic chemistry and biochemistry, a side chain is a chemical group that is attached to a core part of the molecule called the "main chain" or backbone. The side chain is a hydrocarbon branching element of a molecule that is attached to a ...

attached in its

chemical structure A chemical structure determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target molecule or other solid. Molecular geometry refers to the spatial arrangement of ...

. Other dibenzazepine TCAs include imipramine (''N''-methyldesipramine), clomipramine,

trimipramine Trimipramine, sold under the brand name Surmontil among others, is a tricyclic antidepressant (TCA) which is used to treat depression. It has also been used for its sedative, anxiolytic, and weak antipsychotic effects in the treatment of insomni ...

, and lofepramine (''N''-(4-chlorobenzoylmethyl)desipramine). Desipramine is a secondary amine TCA, with its ''N''- methylated parent imipramine being a tertiary amine. Other secondary amine TCAs include

and

protriptyline Protriptyline, sold under the brand name Vivactil among others, is a tricyclic antidepressant (TCA), specifically a secondary amine, indicated for the treatment of depression and attention-deficit hyperactivity disorder (ADHD). Uniquely among ...

. The

chemical name A chemical nomenclature is a set of rules to generate systematic names for chemical compounds. The nomenclature used most frequently worldwide is the one created and developed by the International Union of Pure and Applied Chemistry (IUPAC). The ...

of desipramine is 3-(10,11-dihydro-5''H''-dibenzo 'b'',''f''zepin-5-yl)-''N''-methylpropan-1-amine and its free base form has a

chemical formula In chemistry, a chemical formula is a way of presenting information about the chemical proportions of atoms that constitute a particular chemical compound or molecule, using chemical element symbols, numbers, and sometimes also other symbols, ...

of C₁₈H₂₂N₂ with a

molecular weight A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bio ...

of 266.381 g/mol. The drug is used commercially mostly as the

hydrochloride In chemistry, a hydrochloride is an acid salt resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base (e.g. an amine). An alternative name is chlorhydrate, which comes from French. An archaic alternative n ...

salt Salt is a mineral composed primarily of sodium chloride (NaCl), a chemical compound belonging to the larger class of salts; salt in the form of a natural crystalline mineral is known as rock salt or halite. Salt is present in vast quant ...

; the dibudinate salt is or has been used for

intramuscular injection Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles hav ...

Argentina Argentina (), officially the Argentine Republic ( es, link=no, República Argentina), is a country in the southern half of South America. Argentina covers an area of , making it the List of South American countries by area, second-largest ...

(brand name Nebril) and the free base form is not used. The

CAS Registry Number A CAS Registry Number (also referred to as CAS RN or informally CAS Number) is a unique identification number assigned by the Chemical Abstracts Service (CAS), US to every chemical substance described in the open scientific literature. It inclu ...

of the free base is 50-47-5, of the hydrochloride is 58-28-6, and of the dibudinate is 62265-06-9.

History

Desipramine was developed by Geigy. It first appeared in the literature in 1959 and was patented in 1962. The drug was first introduced for the treatment of depression in 1963 or 1964.

Society and culture

Generic names

''Desipramine'' is the generic name of the drug and its and , while ''desipramine hydrochloride'' is its , , , and . Its generic name in

French French (french: français(e), link=no) may refer to: * Something of, from, or related to France ** French language, which originated in France, and its various dialects and accents ** French people, a nation and ethnic group identified with Franc ...

and its are ''désipramine'', in

Spanish Spanish might refer to: * Items from or related to Spain: **Spaniards are a nation and ethnic group indigenous to Spain **Spanish language, spoken in Spain and many Latin American countries **Spanish cuisine Other places * Spanish, Ontario, Can ...

and

Italian Italian(s) may refer to: * Anything of, from, or related to the people of Italy over the centuries ** Italians, an ethnic group or simply a citizen of the Italian Republic or Italian Kingdom ** Italian language, a Romance language *** Regional Ita ...

and its are ''desipramina'', in

German German(s) may refer to: * Germany (of or related to) **Germania (historical use) * Germans, citizens of Germany, people of German ancestry, or native speakers of the German language ** For citizens of Germany, see also German nationality law **Ge ...

is ''desipramin'', and in

Latin Latin (, or , ) is a classical language belonging to the Italic languages, Italic branch of the Indo-European languages. Latin was originally a dialect spoken in the lower Tiber area (then known as Latium) around present-day Rome, but through ...

is ''desipraminum''.

Brand names

Desipramine is or has been marketed throughout the world under a variety of brand names, including Irene, Nebril, Norpramin, Pertofran, Pertofrane, Pertrofran, and Petylyl among others.

References

External links

Desipramine - MedlinePlus
{{Tricyclics Alpha-1 blockers Antihistamines CYP2D6 inhibitors Dibenzazepines Human drug metabolites Muscarinic antagonists Norepinephrine reuptake inhibitors Secondary amines Serotonin receptor antagonists Sodium channel blockers Stimulants Tricyclic antidepressants