5-Chloro-α-methyltryptamine (5-Chloro-αMT), also known as PAL-542, is a

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 f ...

derivative In mathematics, the derivative of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. ...

related to α-methyltryptamine (αMT) and one of only a few known specific serotonin-dopamine releasing agents (SDRAs). It has been investigated in animals as a potential treatment for

cocaine dependence Cocaine dependence is a neurological disorder that is characterized by withdrawal symptoms upon cessation from cocaine use. It also often coincides with cocaine addiction which is a biopsychosocial disorder characterized by persistent use of coc ...

. The EC₅₀ values of 5-chloro-αMT in evoking the ''

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

release Release may refer to: * Art release, the public distribution of an artistic production, such as a film, album, or song * Legal release, a legal instrument * News release, a communication directed at the news media * Release (ISUP), a code to iden ...

of serotonin (5-HT), dopamine (DA), and

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad' ...

(NE) in rat synaptosomes were reported as 16 nM, 54 nM, and 3434 nM, with an NE/DA ratio of 63.6 and a DA/5-HT ratio of 3.38, indicating that it is a highly specific and well-balanced SDRA. However, 5-chloro-αMT has also been found to act as a potent

full agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the a ...

of the 5-HT_2A receptor, with an EC₅₀ value of 6.27 nM and an efficacy of 105%, and almost assuredly acts as a potent agonist of other serotonin receptors as well. 5-Chloro-αMT was found to not reliably produce

intracranial The cranial cavity, also known as intracranial space, is the space within the skull that accommodates the brain. The skull minus the mandible is called the ''cranium''. The cavity is formed by eight cranial bones known as the neurocranium that in ...

self-administration in rats or substitute for

cocaine Cocaine (from , from , ultimately from Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly used recreationally for its euphoric effects. It is primarily obtained from the leaves of two Coca species native to South Ameri ...

in rats or monkeys. It was found through study of 5-chloro-αMT in rhesus monkeys that norepinephrine release has minimal influence on the

abuse potential Substance abuse, also known as drug abuse, is the use of a drug in amounts or by methods which are harmful to the individual or others. It is a form of substance-related disorder. Differing definitions of drug abuse are used in public health, ...

monoamine releasing agent A monoamine releasing agent (MRA), or simply monoamine releaser, is a drug that induces the release of a monoamine neurotransmitter from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of th ...

s and that loss of norepinephrine release activity does not affect efficacy in reducing cocaine self-administration in SDRAs relative to serotonin-norepinephrine-dopamine releasing agents (SNDRAs) such as

naphthylisopropylamine Naphthylaminopropane (PAL-287) is an experimental drug under investigation as of 2007 for the treatment of alcohol and stimulant addiction. Naphthylisopropylamine acts as a non-neurotoxic releasing agent of serotonin, norepinephrine, and dopamin ...

(PAL-287). However, SDRAs like PAL-542 would, in theory, be expected to produce fewer

side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

s (including sympathomimetic/

cardiovascular The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...

effects,

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

hyperthermia Hyperthermia, also known simply 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 ...

, and

anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...

) relative to SNDRAs, and thus would likely be comparatively more favorable in the treatment of cocaine dependence and other conditions. A related agent,

5-fluoro-α-methyltryptamine 5-Fluoro-α-methyltryptamine (5-Fluoro-αMT, 5F-AMT), also known as PAL-544, is a putative stimulant, entactogen, and psychedelic drug, psychedelic tryptamine chemical derivative, derivative related to α-methyltryptamine (αMT). It has been foun ...

(5-fluoro-αMT), also known as PAL-544, is a potent MAO-A inhibitor in addition to SNDRA and 5-HT_2A receptor agonist. Due to their close

structural A structure is an arrangement and organization of interrelated elements in a material object or system, or the object or system so organized. Material structures include man-made objects such as buildings and machines and natural objects such ...

similarity, 5-chloro-αMT might also possess activity as an MAO-A inhibitor, a property which, in combination with its activity as

, could potentially render it dangerous in an analogous manner to the phenethylamine derivative ''para''-methoxyamphetamine (PMA). In addition, α-ethyltryptamine (αET), an SNDRA and close

structural analogue A structural analog (analogue in modern traditional English; Commonwealth English), also known as a chemical analog or simply an analog, is a compound having a structure similar to that of another compound, but differing from it in respect to a ce ...

of αMT and 5-chloro-αMT, like many other

releasing agent A monoamine releasing agent (MRA), or simply monoamine releaser, is a drug that induces the synapse, release of a monoamine neurotransmitter from the synapse, presynaptic neuron into the synapse, leading to an increase in the extracellular conc ...

s of both 5-HT and DA such as

MDMA 3,4-Methylenedioxymethamphetamine (MDMA), commonly seen in tablet form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for recreational purposes. The desire ...

, has been found to produce long-lasting

serotonergic Serotonergic () or serotoninergic () means "pertaining to or affecting serotonin". Serotonin is a neurotransmitter. A synapse is serotonergic if it uses serotonin as its neurotransmitter. A serotonergic neuron ''produces'' serotonin. A substance is ...

neurotoxicity Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specificall ...

in rats, and the same could also prove true for 5-chloro-αMT and other monoamine-releasing tryptamines. As a 5-HT_2A receptor agonist, 5-chloro-αMT very likely possesses the capacity for psychedelic effects. Indeed, its close analog 5-fluoro-αMT produces a strong

head-twitch response The head-twitch response (HTR) is a rapid side-to-side head movement that occurs in mice and rats after the serotonin 5-HT2A receptor is activated. The prefrontal cortex may be the neuroanatomical locus mediating the HTR. Many serotonergic hallucino ...

in rats, a property which is highly correlated with psychedelic effects in humans, and αMT is well-established as a psychedelic drug in humans.

Legality

5-Chloro-AMT is illegal in Singapore.

References

{{DEFAULTSORT:Chloro-alphaMT 5-HT2A agonists Entactogens and empathogens Chloroarenes Psychedelic tryptamines Serotonin-dopamine releasing agents Serotonin receptor agonists Stimulants

Legality

See also

References