5-(2-Aminopropyl)indole (5-API, 5-IT, PAL-571) is an

indole Indole is an organic compound with the formula . Indole is classified as an aromatic heterocycle. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered pyrrole ring. Indoles are derivatives of indole ...

and

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 ...

derivative with empathogenic effects. Its preparation was first reported by

Albert Hofmann Albert Hofmann (11 January 1906 – 29 April 2008) was a Swiss chemist known for being the first to synthesize, ingest, and learn of the psychedelic effects of lysergic acid diethylamide (LSD). Hofmann's team also isolated, named and synthesi ...

in 1962. It is a

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. ...

that has been openly sold as a

recreational drug Recreational drug use is the use of one or more psychoactive drugs to induce an altered state of consciousness, either for pleasure or for some other casual purpose or pastime. When a psychoactive drug enters the user's body, it induces an Sub ...

by online vendors since 2011.

Chemistry

Although 5-IT is a

positional isomer In chemistry, a structural isomer (or constitutional isomer in the IUPAC nomenclature) of a compound is a compound that contains the same number and type of atoms, but with a different connectivity (i.e. arrangement of bonds) between them. The ...

of the

tryptamine Tryptamine is an indolamine metabolite of the essential amino acid tryptophan. The chemical structure is defined by an indole—a fused benzene and pyrrole ring, and a 2-aminoethyl group at the second carbon (third aromatic atom, with the firs ...

drug αMT, the compound is not itself a tryptamine as the indole ring is substituted at the 5 position rather than at the 3 position. The compound is closer chemically to phenethylamine derivatives such as

5-APB 5-APB (abbreviation of "5-(2-aminopropyl)benzofuran") is an empathogenic psychoactive compound of the phenethylamine, amphetamine, and benzofuran families. The drug and other compounds have sometimes been informally called "Benzofury". 5-APB ha ...

. This is reflected in the compound's effects when used as a drug, which are reportedly stimulating rather than psychedelic.

Pharmacology

5-IT acts as a

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 ...

(SNDRA) with values of 12.9nM for

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

, 13.3nM for

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

, and 104.8nM for

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, ...

, and is also an MAO-A inhibitor, with an of 200 to 1,600nM. Additional molecular target data have also been reported for 5-IT, including

serotonin receptor 5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in multiple tissues including the central and peripheral nervous systems. They mediate both ex ...

interactions.

Dosage and effects

Alexander Shulgin Alexander Theodore "Sasha" Shulgin (June 17, 1925 – June 2, 2014) was an American biochemist, broad researcher of synthetic psychoactive compounds, and author of works regarding these, who independently explored the organic chemistry and ph ...

wrote briefly about 5-IT in ''

TiHKAL ''TiHKAL: The Continuation'' is a 1997 book written by Alexander Shulgin and Ann Shulgin about a family of psychoactive drugs known as tryptamines. A sequel to '' PiHKAL: A Chemical Love Story'', ''TiHKAL'' is an acronym that stands for "Trypt ...

'' saying: "at 20 milligrams orally, tis a long-lived stimulant producing increased heart-rate, anorexia, diuresis, and slight hyperthermia for about twelve hours." As 5-IT is not a tryptamine and thus not within the scope of the book, it is not discussed in any more detail than this. The following symptoms can indicate 5-IT has been ingested:

hyperthermia Hyperthermia, also known as overheating, is a condition in which an individual's body temperature is elevated beyond normal due to failed thermoregulation. The person's body produces or absorbs more heat than it dissipates. When extreme te ...

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ...

, increased blood pressure, dilated pupils (mydriasis), agitation, excessive

sweat Perspiration, also known as sweat, is the fluid secreted by sweat glands in the skin of mammals. Two types of sweat glands can be found in humans: eccrine glands and Apocrine sweat gland, apocrine glands. The eccrine sweat glands are distribu ...

ing, jaw clenching,

insomnia Insomnia, also known as sleeplessness, is a sleep disorder where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ...

disorientation Orientation is a function of the mind involving awareness of three dimensions: time, place and person. Problems with orientation lead to ''dis''orientation, and can be due to various conditions. It ranges from an inability to coherently understand ...

, restlessness,

anxiety Anxiety is an emotion characterised by an unpleasant state of inner wikt:turmoil, turmoil and includes feelings of dread over Anticipation, anticipated events. Anxiety is different from fear in that fear is defined as the emotional response ...

, and

tremor A tremor is an involuntary, somewhat rhythmic muscle contraction and relaxation involving neural oscillations, oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the h ...

. It is a MAOI, and when combined with a contraindicated substance, it can lead to death.

Deaths

5-IT has been attributed to 14 deaths of people in Sweden since its discovery. 5-IT was listed as the sole intoxicant in two cases but other drugs were also found in the twelve other

post mortem An autopsy (also referred to as post-mortem examination, obduction, necropsy, or autopsia cadaverum) is a surgical procedure that consists of a thorough examination of a corpse by dissection to determine the cause, mode, and manner of death; ...

examinations. The 14 deaths occurred between April and July 2012, but a definitive identification of 5-IT in the post-mortem samples was not made until July. All of the dead were young men aged between 20 and 30. Eleven non-fatal poisonings due to 5-IT also reportedly occurred during the same time period.

Legality

* 5-IT is a positional isomer of αMT, and as such is considered legally the same as αMT under the

Controlled Substances Act The Controlled Substances Act (CSA) is the statute establishing federal government of the United States, federal drug policy of the United States, U.S. drug policy under which the manufacture, importation, possession, use, and distribution of ...

in the US. (The Federal Analog Act includes a clause concerning the effects of the substance as well.) * 5-IT was banned as a

temporary class drug A temporary class drug is a relatively new status for controlled drugs, which has been adopted in some jurisdictions, notably New Zealand and the United Kingdom, to attempt to bring newly synthesised designer drugs under legal control. The contro ...

in June 2013, along with 9 other related compounds. On March 5, 2014, the UK Home Office announced that 5-API would be made a class B drug on 10 June 2014 alongside every other benzofuran entactogen and many structurally related drugs. * 5-IT is covered by the Australian analogue act as an analogue of MDA "by the replacement of up to 2 carbocyclic or heterocyclic ring structures with different carbocyclic or heterocyclic ring structures". * A formal application for 5-IT to be made illegal in Sweden was made on July 26, 2012, but did not come into effect immediately. * 5-IT was made illegal in Denmark on 30 September 2012. * 5-IT is an

Anlage I The following drugs are controlled by the German Narcotic Drugs Act ( or ). Trade and possession of these substances without licence or prescription is considered illegal; prescription is illegal for drugs on ''Anlage I'' and II and drugs on ''Anl ...

controlled drug in Germany. * The European Commission published a proposal for a decision calling upon its member states to take measures to control 5-(2-aminopropyl)indole. It asked member states to introduce control measures and criminal penalties as provided under their national legislation covering psychotropic substances.

References