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 * opipramol * tianeptine * ...

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

trazodone Trazodone is an antidepressant medication used to treat major depressive disorder, anxiety disorders, and insomnia. It is a phenylpiperazine compound of the serotonin antagonist and reuptake inhibitor (SARI) class. The medication is taken or ...

and nefazodone in

chemical structure A chemical structure of a molecule is a spatial arrangement of its atoms and their chemical bonds. Its determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target m ...

and is a serotonin antagonist and reuptake inhibitor (SARI) similarly to them.

Medical uses

Etoperidone was used or was intended for use as an antidepressant in the treatment of depression. Etoperidone might be useful as a hallucinogen antidote or "trip killer" in blocking the effects of

serotonergic psychedelic Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states (known as psychedelic experiences or "trips") and a perceived "expansion of consciousness". Also referred to as classic halluci ...

s like

psilocybin Psilocybin, also known as 4-phosphoryloxy-''N'',''N''-dimethyltryptamine (4-PO-DMT), is a natural product, naturally occurring tryptamine alkaloid and Investigational New Drug, investigational drug found in more than List of psilocybin mushroom ...

and

lysergic acid diethylamide Lysergic acid diethylamide, commonly known as LSD (from German ; often referred to as acid or lucy), is a Semisynthesis, semisynthetic, Hallucinogen, hallucinogenic compound derived from ergot, known for its powerful psychological effects and ...

(LSD).

Pharmacology

Pharmacodynamics

Etoperidone is as an

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.receptors Receptor may refer to: *Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds ...

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 ho ...

: 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 (biochemistry), receptor, but have only partial Intrinsic activity, efficacy at the receptor relative to a full agonist. They may also be considered Ligand (bio ...

) > 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 Pa ...

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 t ...

(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 (DAT, also sodium-dependent dopamine transporter) is a membrane-spanning protein coded for in humans by the ''SLC6A3'' gene (also known as ''DAT1''), that pumps the neurotransmitter dopamine out of the synaptic cleft ba ...

(52,000 nM).

Pharmacokinetics

Etoperidone is

metabolized Metabolism (, from ''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 cellular processes; the co ...

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

Chemistry

Etoperidone is a phenylpiperazine and is chemically related to nefazodone and

History

Etoperidone was discovered by scientists at Angelini, 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 Spain, or the Kingdom of Spain, is a country in Southern Europe, Southern and Western Europe with territories in North Africa. Featuring the Punta de Tarifa, southernmost point of continental Europe, it is the largest country in Southern Eur ...

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

Italy Italy, officially the Italian Republic, is a country in Southern Europe, Southern and Western Europe, Western Europe. It consists of Italian Peninsula, a peninsula that extends into the Mediterranean Sea, with the Alps on its northern land b ...

(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 L.P., formerly IBM Watson Health, is an American medical technology company that provides products and services that help clients facilitate medical research, clinical research, real world evidence, and healthcare services, through the ...

'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 syndrome associated with many neurodegenerative diseases, characterized by a general decline in cognitive abilities that affects a person's ability to perform activities of daily living, everyday activities. This typically invo ...

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 worldwid ...

References

External links

* {{Navboxes , title =

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

, 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 3-Chlorophenyl compounds 1-Phenylpiperazines 1,2,4-Triazol-3-ones Serotonin reuptake inhibitors Ureas