Etoperidone, associated with several brand names, is an

atypical antidepressant An atypical antidepressant is any antidepressant medication that acts in a manner that is different from that of most other antidepressants. Atypical antidepressants include agomelatine, bupropion, iprindole, mianserin, mirtazapine, nefazod ...

which was developed in the 1970s and either is no longer marketed or was never marketed. It is a

phenylpiperazine 1-Phenylpiperazine is a simple chemical compound featuring a phenyl group bound to a piperazine ring. The suffix ‘-piprazole’ is sometimes used in the names of drugs to indicate they belong to this class. List phenylpiperazine derivativesAlp ...

related to

trazodone Trazodone, sold under many brand names, is an antidepressant medication. It is used to treat major depressive disorder, anxiety disorders, and difficulties with sleep. The medication is taken orally. Common side-effects include dry mouth, fe ...

and

nefazodone Nefazodone, sold formerly under the brand names Serzone, Dutonin, and Nefadar among others, is an atypical antidepressant which was first marketed by Bristol-Myers Squibb (BMS) in 1994 but has since largely been discontinued. BMS withdrew it from ...

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 at ...

and is a

serotonin antagonist and reuptake inhibitor Serotonin antagonist and reuptake inhibitors (SARIs) are a class of drugs used mainly as antidepressants, but also as anxiolytics and hypnotics. They act by antagonizing serotonin receptors such as 5-HT2A and inhibiting the reuptake of s ...

(SARI) similarly to them.

Medical uses

Etoperidone was used or was intended for use as an antidepressant in the treatment of depression.

Pharmacology

Pharmacodynamics

Etoperidone is as an

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

of several

receptors Receptor may refer to: *Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a n ...

in the following order of

potency Potency may refer to: * Potency (pharmacology), a measure of the activity of a drug in a biological system * Virility * Cell potency, a measure of the differentiation potential of stem cells * In homeopathic dilutions, potency is a measure of how ...

: 5-HT_2A receptor (36 nM) > α₁-adrenergic receptor (38 nM) > 5-HT_1A receptor (85 nM) (may be a

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonistic e ...

) > α₂-adrenergic receptor (570 nM); it has only very weak or negligible

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Par ...

for blocking the following receptors: D₂ receptor (2,300 nM) > H₁ receptor (3,100 nM) > mACh receptors (>35,000 nM). In addition to its receptor blockade, etoperidone also has weak affinity for the

monoamine Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin. All monoamines are ...

transporters as well:

serotonin transporter The serotonin transporter (SERT or 5-HTT) also known as the sodium-dependent serotonin transporter and solute carrier family 6 member 4 is a protein that in humans is encoded by the SLC6A4 gene. SERT is a type of monoamine transporter protein tha ...

(890 nM) >

norepinephrine transporter The norepinephrine transporter (NET), also known as noradrenaline transporter (NAT), is a protein that in humans is encoded by the solute carrier family 6 member 2 (SLC6A2) gene. NET is a monoamine transporter and is responsible for the sodium- ...

(20,000 nM) >

dopamine transporter The dopamine transporter (also dopamine active transporter, DAT, SLC6A3) is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synaptic cleft back into cytosol. In the cytosol, other transporters sequester the dopam ...

(52,000 nM).

Pharmacokinetics

Etoperidone is

metabolized Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

in part to ''meta''-chlorophenylpiperazine (mCPP), which likely accounts for its

serotonergic Serotonergic () or serotoninergic () means "pertaining to or affecting serotonin". Serotonin is a neurotransmitter. A synapse is serotonergic if it uses serotonin as its neurotransmitter. A serotonergic neuron ''produces'' serotonin. A substance is ...

effects.

Chemistry

Etoperidone is a

and is chemically related to

and

History

Etoperidone was discovered by scientists at

Angelini Angelini is a medium-sized private international group. Founded in Italy in the early twentieth century, the Angelini group has offices in 25 countries. Led by President Francesco Angelini, the industrial group employs approximately 3000 people. ...

, who also discovered trazodone. Its development names have included ST-1191 and McN-A-2673-11. The ''etoperidone'' was proposed in 1976 and recommended in 1977. The drug was given brand names in

Spain , image_flag = Bandera de España.svg , image_coat = Escudo de España (mazonado).svg , national_motto = ''Plus ultra'' (Latin)(English: "Further Beyond") , national_anthem = (English: "Royal March") , i ...

(Centren (Esteve) and Depraser (Lepori)) and

Italy Italy ( it, Italia ), officially the Italian Republic, ) or the Republic of Italy, is a country in Southern Europe. It is located in the middle of the Mediterranean Sea, and its territory largely coincides with the homonymous geographical re ...

(Staff (Sigma Tau)) and was also given the brand names Axiomin and Etonin, but it is not entirely clear if it was actually marketed; the Pharmaceutical Manufacturing Encyclopedia provides no dates for commercial introduction. According to

Micromedex Merative, formerly IBM Watson Health, is a standalone company as of 2022. Merative offers products and services that help clients facilitate medical research, clinical research, Real world evidence, and healthcare services, through the use of ar ...

's Index Nominum: International Drug Directory, etoperidone was indeed previously marketed in Spain and Italy.

Society and culture

Generic names

''Etoperidone'' is the generic name of the drug and its , while ''etoperidone hydrochloride'' is its .

Brand names

Etoperidone has been associated with the brand names Axiomin, Centren, Depraser, Etonin, and Staff.

Research

Etoperidone has been studied in

dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...

and found to be about as effective as

thioridazine Thioridazine (Mellaril or Melleril) is a first generation antipsychotic drug belonging to the phenothiazine drug group and was previously widely used in the treatment of schizophrenia and psychosis. The branded product was withdrawn worldwide ...

References

External links

* {{Navboxes , title =

Pharmacodynamics Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms (fo ...

, titlestyle = background:#ccccff , list1 = {{Adrenergic receptor modulators {{Monoamine reuptake inhibitors {{Serotonin receptor modulators 5-HT2A antagonists Abandoned drugs Alpha-1 blockers Alpha-2 blockers Antidepressants Anxiolytics 2-(3-(4-(3-chlorophenyl)piperazin-1-yl)propyl)-1,2,4-triazol-3-ones Serotonin reuptake inhibitors Ureas