Amoxapine is a tetracyclic antidepressant

Tetracyclic antidepressant

Tetracyclic antidepressants are a class of drugs used primarily as antidepressants that were first introduced in the 1970s. They are named after their chemical structure which contains four rings of atoms and are closely related to the tricyclic antidepressants which contain three rings of...

 of the dibenzoxazepine family, though it is often classified as a secondary amine tricyclic antidepressant

Tricyclic antidepressant

Tricyclic antidepressants are heterocyclic chemical compounds used primarily as antidepressants. The TCAs were first discovered in the early 1950s and were subsequently introduced later in the decade; they are named after their chemical structure, which contains three rings of atoms...

.

Uses

Amoxapine is used in the treatment of depression

Clinical depression

Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...

, anxiety disorder

Anxiety disorder

Anxiety disorder is a blanket term covering several different forms of abnormal and pathological fear and anxiety. Conditions now considered anxiety disorders only came under the aegis of psychiatry at the end of the 19th century. Gelder, Mayou & Geddes explains that anxiety disorders are...

s, panic disorder

Panic disorder

Panic disorder is an anxiety disorder characterized by recurring severe panic attacks. It may also include significant behavioral change lasting at least a month and of ongoing worry about the implications or concern about having other attacks. The latter are called anticipatory attacks...

, and bipolar disorder

Bipolar disorder

Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...

. It also has properties similar to those of atypical antipsychotic

Atypical antipsychotic

The atypical antipsychotics are a group of antipsychotic tranquilizing drugs used to treat psychiatric conditions. Some atypical antipsychotics are FDA approved for use in the treatment of schizophrenia...

, and may be used in the treatment of schizophrenic psychosis

Psychosis

Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...

 off-label.

Pharmacology

Amoxapine possesses a wide array of pharmacological effects. It is a moderate and strong reuptake inhibitor

Reuptake inhibitor

A reuptake inhibitor , also known as a transporter blocker, is a drug that inhibits the plasmalemmal transporter-mediated reuptake of a neurotransmitter from the synapse into the pre-synaptic neuron, leading to an increase in the extracellular concentrations of the neurotransmitter and therefore an...

 of serotonin

Serotonin

Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

 and norepinephrine

Norepinephrine

Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...

, respectively, and binds to the 5-HT_2A

5-HT2A receptor

The mammalian 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor . This is the main excitatory receptor subtype among the GPCRs for serotonin , although 5-HT2A may also have an inhibitory effect on certain areas such...

, 5-HT_2B

5-HT2B receptor

5-hydroxytryptamine receptor 2B, also known as HTR2B, is a 5-HT2 receptor, but also denotes the human gene encoding it.-Function:...

, 5-HT_2C

5-HT2C receptor

The 5-HT2C receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin . It is a G protein-coupled receptor that is coupled to Gq/G11 and mediates excitatory neurotransmission. HTR2C denotes the human gene encoding for the receptor, that in humans is located at the...

, 5-HT₃

5-HT3 receptor

The 5-HT3 receptor is a member of the superfamily of ligand-gated ion channels, a superfamily that also includes the neuronal nicotinic acetylcholine receptors , and the inhibitory neurotransmitter receptors for GABA and glycine...

, 5-HT₆

5-HT6 receptor

The 5-HT6 receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin . It is a G protein-coupled receptor that is coupled to Gs/Go and mediates excitatory neurotransmission. HTR6 denotes the human gene encoding for the receptor.-Distribution:The 5-HT6 receptor is...

, 5-HT₇

5-HT7 receptor

The 5-HT7 receptor is a member of the GPCR superfamily of cell surface receptors and is activated by the neurotransmitter serotonin The 5-HT7 receptor is coupled to Gs and is expressed in a variety of human tissues, particularly in the brain, the gastrointestinal tract, and in various...

, D₂, α₁-adrenergic

Alpha-1 adrenergic receptor

The alpha-1 adrenergic receptor is a G protein-coupled receptor associated with the Gq heterotrimeric G-protein. It consists of three highly homologous subtypes, including α1A-, α1B-, and α1D-adrenergic...

, D₃, D₄, and H₁ receptor

H1 receptor

The H1 receptor is a histamine receptor belonging to the family of Rhodopsin like G-protein-coupled receptors. This receptor, which is activated by the biogenic amine histamine, is expressed throughout the body, to be specific, in smooth muscles, on vascular endothelial cells, in the heart, and in...

s with varying but significant affinity, where it acts as an antagonist

Receptor antagonist

A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...

 (or inverse agonist

Inverse agonist

In the field of pharmacology, an inverse agonist is an agent that binds to the same receptor as an agonist but induces a pharmacological response opposite to that agonist....

 depending on the receptor in question) at all sites. It has weak but negligible affinity for the dopamine transporter

Dopamine transporter

The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

 and the 5-HT_1A

5-HT1A receptor

The 5-HT1A receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin . It is a G protein-coupled receptor that is coupled to Gi/Go and mediates inhibitory neurotransmission...

, 5-HT_1B

5-HT1B receptor

5-hydroxytryptamine receptor 1B also known as the 5-HT1B receptor is a protein that in humans is encoded by the HTR1B gene. The 5-HT1B receptor is a 5-HT receptor subtype.-Tissue distribution and function:...

, D₁, α₂-adrenergic

Alpha-2 adrenergic receptor

The alpha-2 adrenergic receptor is a G protein-coupled receptor associated with the Gi heterotrimeric G-protein. It consists of three highly homologous subtypes, including α2A-, α2B-, and α2C-adrenergic. Some species other than humans express a fourth α2D-adrenergic receptor as well...

, H₄

H4 receptor

The histamine H4 receptor is, like the other three histamine receptors, a member of the G protein-coupled receptor superfamily.-Tissue distribution:...

, mACh

Muscarinic acetylcholine receptor

Muscarinic receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled in the plasma membranes of certain neurons and other cells...

, and GABA_A receptors, and no affinity for the β-adrenergic receptors or the allosteric

Allosteric regulation

In biochemistry, allosteric regulation is the regulation of an enzyme or other protein by binding an effector molecule at the protein's allosteric site . Effectors that enhance the protein's activity are referred to as allosteric activators, whereas those that decrease the protein's activity are...

 benzodiazepine site on the GABA_A receptor.

7-Hydroxyamoxapine

7-Hydroxyamoxapine

7-Hydroxyamoxapine is a metabolite of amoxapine.- References :...

, a major active metabolite

Active metabolite

- Prodrugs :Sometimes drugs are formulated deliberately so they will break down inside the body to form the active drug, these are called prodrugs. The reason for this may be because the drug is more stable during manufacture and storage as the prodrug form, or because the prodrug is better...

 of amoxapine, is a more potent

Potency (pharmacology)

In the field of pharmacology, potency is a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity. A highly potent drug evokes a larger response at low concentrations, while a drug of lower potency evokes a small response at low concentrations...

 dopamine receptor

Dopamine receptor

Dopamine receptors are a class of metabotropic G protein-coupled receptors that are prominent in the vertebrate central nervous system . The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors....

 antagonist and contributes to its neuroleptic efficacy, whereas 8-hydroxyamoxapine is a norepinephrine reuptake inhibitor

Norepinephrine reuptake inhibitor

A norepinephrine reuptake inhibitor or adrenergic reuptake inhibitor , is a type of drug which acts as a reuptake inhibitor for the neurotransmitters norepinephrine and epinephrine by blocking the action of the norepinephrine transporter...

 but a stronger serotonin reuptake inhibitor and helps to balance amoxapine's ratio of serotonin

Serotonin transporter

The serotonin transporter is a monoamine transporter protein.This protein is an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it...

 to norepinephrine transporter

Norepinephrine transporter

The norepinephrine transporter , also known as solute carrier family 6 member 2 , is a protein that in humans is encoded by the SLC6A2 gene....

 blockade.

Side effects

Common side effect

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, consequences of the use of a drug.Occasionally, drugs are...

s of amoxapine include hypotension

Hypotension

In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...

, drowsiness, dry mouth, constipation

Constipation

Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...

, blurred vision

Blurred vision

-Causes:There are many causes of blurred vision:* Use of atropine or other anticholinergics* Presbyopia -- Difficulty focusing on objects that are close. The elderly are common victims....

, fatigue

Fatigue

Fatigue may refer to:*Fatigue , structural damage from repeated loading*Fatigue , a state of physical and/or mental weakness*Fatigue , safety implications of tiredness...

, and vertigo

Vertigo

Vertigo is a form of dizziness.Vertigo may also refer to:* Vertigo , a 1958 film by Alfred Hitchcock**Vertigo , its soundtrack** Vertigo effect, or Dolly zoom, a special effect in film, named after the movie...

. Additionally, due to the drug's and its metabolite 7-hyroxyamoxapine's potent blockade of dopamine receptors, it can cause neuroleptic malignant syndrome

Neuroleptic malignant syndrome

Neuroleptic malignant syndrome is a life- threatening neurological disorder most often caused by an adverse reaction to neuroleptic or antipsychotic drugs...

 as well as acute extrapyramidal symptoms

Extrapyramidal symptoms

The extrapyramidal system can be affected in a number of ways, which are revealed in a range of extrapyramidal symptoms , also known as extrapyramidal side-effects , such as akinesia and akathisia .Extrapyramidal symptoms are various movement disorders such as acute dystonic reactions,...

 and tardive dyskinesia

Tardive dyskinesia

Tardive dyskinesia is a difficult-to-treat form of dyskinesia that can be tardive...

. Cardiovascular and anticholinergic

Anticholinergic

An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is dicycloverine, and the classic example is atropine....

side effects are much reduced compared to other tri- and tetracyclic antidepressants.

Contraindications

The drug is contraindicated in children because it lowers the seizure threshold to the extent that fits may be precipitated.