The substituted benzothiophenes are a class of

chemical compound A chemical compound is a chemical substance composed of many identical molecules (or molecular entities) containing atoms from more than one chemical element held together by chemical bonds. A molecule consisting of atoms of only one element ...

s based on

benzothiophene Benzothiophene is an aromatic organic compound with a molecular formula C8H6S and an odor similar to naphthalene (mothballs). It occurs naturally as a constituent of petroleum-related deposits such as lignite tar. Benzothiophene has no househol ...

. They are closely related to the

substituted benzofuran The substituted benzofurans are a class of chemical compounds based on the heterocyclic compound, heterocyclic and polycyclic compound, polycyclic compound benzofuran. Many medicines use the benzofuran core as a scaffold, but most commonly the t ...

substituted tryptamine Substituted tryptamines, or simply tryptamines, also known as serotonin analogues (i.e., 5-hydroxytryptamine analogues), are organic compounds which may be thought of as being derived from tryptamine itself. The molecular structures of all trypt ...

s, and to other

chemical group In organic chemistry, a functional group is any substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the re ...

s such as the substituted benzodioxoles (or

methylenedioxy Methylenedioxy is the term used in the field of chemistry, particularly in organic chemistry, for a functional group with the structural formula which is connected to the rest of a molecule by two chemical bonds. The methylenedioxy group consist ...

phenyl In organic chemistry, the phenyl group, or phenyl ring, is a cyclic group of atoms with the formula , and is often represented by the symbol Ph (archaically φ) or Ø. The phenyl group is closely related to benzene and can be viewed as a benzene ...

compounds). Substituted benzothiophenes include the (2-aminopropyl)benzo �hiophenes (APBTs)

2-APBT 2-APBT is a monoamine releasing agent (MRA) of the benzothiophene family. It acts specifically as a fairly well-balanced serotonin–norepinephrine–dopamine releasing agent (SNDRA), with values of 8.9nM for serotonin, 21.6nM for norepinephrine, ...

3-APBT 3-APBT (former developmental code name SKF-6678), also known as 3-(2-aminopropyl)benzo �hiophene, is a monoamine releasing agent and serotonin receptor agonist of the benzothiophene group. It is an analogue of α-methyltryptamine (AMT) in which ...

(SKF-6678),

4-APBT 4-APBT, also known as 4-(2-aminopropyl)-1-benzothiophene, is a monoamine releasing agent (MRA) of the amphetamine and benzothiophene families. It acts specifically as a fairly well-balanced serotonin–norepinephrine–dopamine releasing agent (SN ...

5-APBT 5-(2-Aminopropyl)-1-benzothiophene (5-APBT) is a monoamine releasing agent and serotonin receptor agonist of the amphetamine and benzothiophene families. It is related to MDA and other MDA bioisosteres like the benzofurans. The drug acts as a ...

5-MAPBT 5-MAPBT (5-methylaminopropylbenzothiophene) is an empathogenic drug of the benzothiophene group. It is closely related to 5-MAPB but with the oxygen atom replaced by sulfur, changing the core ring structure to benzothiophene rather than benzofura ...

6-APBT 6-(2-Aminopropyl)-1-benzothiophene (6-APBT) is a monoamine releasing agent and serotonin receptor agonist of the amphetamine and benzothiophene families. It is related to MDA and other MDA bioisosteres like the benzofurans. The drug acts as a ...

, 6-MAPBT, and

7-APBT 7-APBT is a monoamine releasing agent (MRA) of the amphetamine and benzothiophene families. It acts specifically as a fairly well-balanced serotonin–norepinephrine–dopamine releasing agent (SNDRA), with values of 36.9nM for serotonin, 28.5nM ...

. These drugs have been found to act as

serotonin–norepinephrine–dopamine releasing agent A serotonin–norepinephrine–dopamine releasing agent (SNDRA), also known as a triple releasing agent (TRA), is a type of drug which induces the release of serotonin, norepinephrine/epinephrine, and dopamine in the brain and body. SNDRAs produc ...

s (SNDRAs) and, in some cases, as potent

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

5-HT₂ receptor

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

s, analogously to the entactogen

MDMA 3,4-Methylenedioxymethamphetamine (MDMA), commonly known as ecstasy (tablet form), and molly (crystal form), is an empathogen–entactogenic drug with stimulant and minor Psychedelic drug, psychedelic properties. In studies, it has been used ...

. They do not produce

hyperlocomotion Locomotor activity is a measure of animal behavior which is employed in scientific research. Hyperlocomotion, also known as locomotor hyperactivity, hyperactivity, or increased locomotor activity, is an effect of certain drugs in animals in whi ...

in rodents, suggesting that they lack

psychostimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition ...

effects. However, those acting as serotonin 5-HT₂ receptor agonists have been found to induce the

head-twitch response The head-twitch response (HTR), also sometimes known as wet dog shakes (WDS) in rats, is a rapid side-to-side head movement that occurs in mice and rats in association with serotonin 5-HT2A receptor activation. Serotonergic psychedelics like lys ...

, a behavioral proxy of

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 ...

effects, in rodents. These findings suggest that substituted benzothiophenes may have entactogenic and/or psychedelic effects in humans whilst lacking stimulant effects and possibly having reduced misuse potential. The substituted benzothiophenes have been little-encountered as

designer drug A designer drug is a structural or functional analog of a controlled substance that has been designed to mimic the pharmacological effects of the original drug, while avoiding classification as illegal and/or detection in standard drug tests. ...

s as of 2022.

Tactogen Tactogen is a public benefit corporation and start-up pharmaceutical company based in Palo Alto, California that is developing novel MDMA-like entactogens and psychedelics as medicines. Its stated goal is to develop new MDMA-like drugs with impr ...

has

patent A patent is a type of intellectual property that gives its owner the legal right to exclude others from making, using, or selling an invention for a limited period of time in exchange for publishing an sufficiency of disclosure, enabling discl ...

ed a number of benzothiophenes as novel entactogens for use as potential medicines.

References

Benzothiophenes Entactogens Monoamine releasing agents Psychedelic drugs Serotonin receptor agonists {{Pharmacology-stub

See also

References