DEMPDHPCA is a

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 ...

and a cyclized

phenethylamine Phenethylamine (PEA) is an organic compound, natural monoamine alkaloid, and trace amine, which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace ami ...

and simplified or partial ergoline that is structurally related to the

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 ...

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). It is the analogue of LSD in which the

carbon Carbon () is a chemical element; it has chemical symbol, symbol C and atomic number 6. It is nonmetallic and tetravalence, tetravalent—meaning that its atoms are able to form up to four covalent bonds due to its valence shell exhibiting 4 ...

and

nitrogen Nitrogen is a chemical element; it has Symbol (chemistry), symbol N and atomic number 7. Nitrogen is a Nonmetal (chemistry), nonmetal and the lightest member of pnictogen, group 15 of the periodic table, often called the Pnictogen, pnictogens. ...

atom Atoms are the basic particles of the chemical elements. An atom consists of a atomic nucleus, nucleus of protons and generally neutrons, surrounded by an electromagnetically bound swarm of electrons. The chemical elements are distinguished fr ...

s at positions 1 through 4 of the

ergoline Ergoline is a core structure in many alkaloids and their synthetic derivatives. Ergoline alkaloids were first characterized in ergot. Some of these are implicated in the condition of ergotism, which can take a convulsive form or a gangrenous for ...

ring system A ring system is a disc or torus orbiting an astronomical object that is composed of solid material such as dust, meteoroids, planetoids, moonlets, or stellar objects. Ring systems are best known as planetary rings, common components of sate ...

have been removed. DEMPDHPCA and LSD structures

Pharmacology

DEMPDHPCA produces gross behavioral effects very similar to those of psychedelics like LSD in rodents and has been assumed to act as a

hallucinogen Hallucinogens, also known as psychedelics, entheogens, or historically as psychotomimetics, are a large and diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mo ...

likewise. However, the drug has not been tested in humans. DEMPDHPCA is much less potent than LSD in rodents, which was active at a dose of 0.16μmol/kg by

intraperitoneal injection Intraperitoneal injection or IP injection is the injection of a substance into the peritoneum (body cavity). It is more often applied to non-human animals than to humans. In general, it is preferred when large amounts of blood replacement fluids ...

, whereas DEMPDHPCA was active at doses of 10 to 35μmol/kg. On the other hand, DEMPDHPCA was more potent than

dimethyltryptamine Dimethyltryptamine (DMT), also known as ''N'',''N''-dimethyltryptamine (''N'',''N''-DMT), is a Psychedelic drug, serotonergic hallucinogen and Investigational New Drug, investigational drug of the substituted tryptamine, tryptamine family tha ...

(DMT) and is more potent than

mescaline Mescaline, also known as mescalin or mezcalin, and in chemical terms 3,4,5-trimethoxyphenethylamine, is a natural product, naturally occurring psychedelic drug, psychedelic alkaloid, protoalkaloid of the substituted phenethylamine class, found ...

. Like LSD, the drug has been found to act as a potent

5-HT_2A and 5-HT_2C receptor

in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

''. The affinities () of the more active

enantiomer In chemistry, an enantiomer (Help:IPA/English, /ɪˈnænti.əmər, ɛ-, -oʊ-/ Help:Pronunciation respelling key, ''ih-NAN-tee-ə-mər''), also known as an optical isomer, antipode, or optical antipode, is one of a pair of molecular entities whi ...

are in the ranges of 10–100nM for the serotonin 5-HT_2A receptor and 100–1,000nM for the serotonin 5-HT_2C receptor, while its activational potencies () are less than 100nM for the serotonin 5-HT_2A receptor and in the range of 10–100nM for the serotonin 5-HT_2C receptor. The more active enantiomer of DEIMDHPCA was among the most potent serotonin 5-HT_2A receptor agonists of 27evaluated ergoline-like compounds.

History

DEMPDHPCA was first described in the

scientific literature Scientific literature encompasses a vast body of academic papers that spans various disciplines within the natural and social sciences. It primarily consists of academic papers that present original empirical research and theoretical ...

by Mangner in 1978. It was subsequently

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 in 2021 by David E. Olson and colleagues and the patent was assigned to Delix Therapeutics.

Derivatives

A few

derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...

s of DEMPDHPCA have also been studied and found to produce similar effects and/or

amphetamine Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...

-like in animals, including the derivatives with 4-

methoxy In organic chemistry, a methoxy group is the functional group consisting of a methyl group bound to oxygen. This alkoxy group has the formula . On a benzene ring, the Hammett equation classifies a methoxy substituent at the ''para'' position a ...

- and 3,4,5-trimethoxy- substitutions on the phenyl ring and the derivative with the phenyl ring replaced with a 1-naphthalene ring. The former two were less potent than DEMPDHPCA, whereas the latter was slightly more potent. Another derivative of DEMPDHPCA, synthesized by David E. Nichols and described in his

thesis A thesis (: theses), or dissertation (abbreviated diss.), is a document submitted in support of candidature for an academic degree or professional qualification presenting the author's research and findings.International Standard ISO 7144: D ...

, is DEMPDHPCA-2C-D, the derivative with 4-

methyl In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula (whereas normal methane has the formula ). In formulas, the group is often abbreviated as ...

and 2,5-dimethoxy substitutions on the phenyl ring.

References

External links

DEMPDHPCA - Isomer Design
{{Ergolines 5-HT2A agonists 5-HT2C agonists Carboxamides Diethylamino compounds Tetrahydropyridines Methyl compounds Partial ergolines Psychedelic phenethylamines

Pharmacology

History

Derivatives

See also

References

External links