2,5-Dimethoxy-4-trifluoromethylamphetamine (DOTFM) is a

psychedelic drug 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 halluc ...

of the

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 ...

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 ...

, and DOx (where 'x' indicates a 4-substitution on the phenyl group of

2,5-dimethoxyamphetamine 2,5-Dimethoxyamphetamine (2,5-DMA), also known as DMA-4 or as DOH, is a drug of the phenethylamine and amphetamine families. It is one of the dimethoxyamphetamine (DMA) series of positional isomers. The drug is notable in being the parent comp ...

) families. It was first synthesized in 1994 by a team at

Purdue University Purdue University is a Public university#United States, public Land-grant university, land-grant research university in West Lafayette, Indiana, United States, and the flagship campus of the Purdue University system. The university was founded ...

led by

David E. Nichols David Earl Nichols (born December 23, 1944, Covington, Kentucky) is an American pharmacologist and medicinal chemist. Previously the Robert C. and Charlotte P. Anderson Distinguished Chair in Pharmacology at Purdue University, Nichols has worke ...

. DOTFM is the α-

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 ...

ated analogue of

2C-TFM 2C-TFM, also known as 4-trifluoromethyl-2,5-dimethoxyphenethylamine, is a serotonin 5-HT2 receptor agonist and psychedelic drug of the phenethylamine and 2C families. It has also been called 2C-CF3, a name derived from the '' para''-trifluorom ...

. It is the most potent DOx psychedelic.

Dosage and effects

According to

Daniel Trachsel Daniel Trachsel is a Swiss people, Swiss chemist who studies psychedelic drug, psychedelics and entactogens. He has developed and published on a large number of novel psychedelic and entactogen chemical compound, compounds, including their psycho ...

, DOTFM is active as a psychedelic in humans at doses of 0.3 to 1mg (300–1,000μg) and its duration is not listed. It is the most potent psychedelic of the DOx family, followed by

DOB DOB or Dob often refers to date of birth. DOB or Dob may also refer to: Biochemistry * 2,5-dimethoxy-4-bromoamphetamine, Bromo-DMA, a psychedelic drug ** Meta-DOB, related substance ** Methyl-DOB, related substance * HLA-DOB, human gene Organiz ...

(dose range 1–3mg).

Pharmacology

DOTFM acts as an

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 ...

at the

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-HT_2A and 5-HT_2C

receptor 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 respond ...

s. In

drug discrimination Drug discrimination (DD) is a technique in behavioral neuroscience used to evaluate the discriminative stimulus properties or interoceptive cues of psychoactive drugs. In drug discrimination, a subject is trained on a training drug, and then i ...

tests in rats, DOTFM fully substituted for

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

and was slightly more potent than DOI. In addition, (''R'')-DOTFM robustly induces 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 effects, in rodents, with equivalent potency as (''R'')-DOI. The drug is around twice as potent as 2C-TFM in

animal studies Animal studies is a recently recognised field in which animals are studied in a variety of cross-disciplinary ways. Scholars who engage in animal studies may be formally trained in a number of diverse fields, including art history, anthropology ...

. In contrast to (''R'')-DOI, which has extraordinarily potent serotonin 5-HT_2A receptor-mediated

anti-inflammatory Anti-inflammatory is the property of a substance or treatment that reduces inflammation, fever or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs reduce pain by inhibiting mechan ...

effects, DOTFM shows no anti-inflammatory effects. The differences between the drugs in this regard appear to be due to differences in

functional selectivity Functional selectivity (or agonist trafficking, biased agonism, biased signaling, ligand bias, and differential engagement) is the ligand-dependent selectivity for certain signal transduction pathways relative to a reference ligand (often the end ...

at the serotonin 5-HT_2A receptor.

References

{{DEFAULTSORT:Dimethoxy-4-trifluoromethylamphetamine, 2,5- 5-HT2A agonists 5-HT2C agonists DOx (psychedelics) Psychedelic phenethylamines Substances discovered in the 1990s Trifluoromethyl compounds

Dosage and effects

Pharmacology

See also

References