Iso-LSD, also known as ''d''-iso-LSD, (+)-iso-LSD, or (5''R''-8''S'')-LSD, as well as ''N'',''N''-diethylisolysergamide, is a

serotonin receptor modulator 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 ...

of the

lysergamide Lysergamides, also known as ergoamides or as lysergic acid amides, are amides of lysergic acid (LA). They are ergolines, with some lysergamides being found naturally in ergot as well as other fungi. Lysergamides are notable in containing embedd ...

family related to

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 8-position

epimer In stereochemistry, an epimer is one of a pair of diastereomers. The two epimers have opposite configuration at only one stereogenic center out of at least two. All other stereogenic centers in the molecules are the same in each. Epimerization is t ...

of LSD, with iso-LSD being 8α (8''S'') and LSD being 8β (8''R''). Iso-LSD is also the ''N'',''N''-diethyl

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 ...

isoergine Isoergine, also known as isolysergic acid amide (iso-LSA or iso-LA-819), isolysergamide, or erginine, is a serotonergic psychedelic of the ergoline and lysergamide families related to ergine (lysergic acid amide; LSA) and lysergic acid diethylami ...

(isolysergic acid amide; iso-LSA), a constituent found in

morning glory Morning glory (also written as morning-glory) is the common name for over 1,000 species of flowering plants in the family Convolvulaceae, whose taxonomy and systematics remain in flux. These species are distributed across numerous genus, gene ...

seeds. Iso-LSD is one of four possible

stereoisomer In stereochemistry, stereoisomerism, or spatial isomerism, is a form of isomerism in which molecules have the same molecular formula and sequence of bonded atoms (constitution), but differ in the three-dimensional orientations of their atoms in ...

s of LSD.

Use and effects

According to

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 ...

and colleagues, iso-LSD is inactive as a

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 ...

in humans at doses of up to 500μg, which is up to 25times the minimum given doses of LSD (i.e., 20–50μg).} In other sources, iso-LSD was also stated as being inactive at doses of up to 50μg/kg (3.5mg for a 70-kg person), whereas LSD is active at a dose of 1μg/kg (70μg for a 70-kg person). Hence, iso-LSD is inactive in humans at doses of up to 50times those of a common psychedelic dose of LSD and at doses of up to 175times the minimum dose of LSD.

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 ...

has additionally reported that iso-LSD was inactive at a dose of 4mg

orally The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid **Oral administration of medicines ** Oral examination (also known as an oral exam or oral ...

. The related drug isoergine is known to be active in terms of

psychoactive A psychoactive drug, psychopharmaceutical, mind-altering drug, consciousness-altering drug, psychoactive substance, or psychotropic substance is a chemical substance that alters psychological functioning by modulating central nervous system acti ...

and

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 ...

ic effects at doses of 2 to 5mg orally.

Pharmacology

Pharmacodynamics

Iso-LSD shows significant

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...

for

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 ...

s. It had an affinity () of about 200nM for serotonin receptors in rat brain membranes. For comparison, LSD had an affinity of about 8 to 10nM in the studies, while isoergine had an affinity of 100 to 200nM and

ergine Ergine, also known as lysergic acid amide (LSA or LAA) as well as LA-111, is a psychoactive compound of the ergoline and lysergamide families related to lysergic acid diethylamide (LSD). Ergine is an ergoline alkaloid found in fungi such as ...

(LSA) had an affinity of about 200nM. Hence, iso-LSD showed about 10- to 30-fold lower affinity for serotonin receptors than LSD but had similar affinity for the receptors as ergine and isoergine. Despite these findings however, iso-LSD showed only 0.12% of the

antiserotonergic A serotonin antagonist, or serotonin receptor antagonist, is a drug used to inhibit the action of serotonin and serotonergic drugs at serotonin (5-HT) receptors. Types 5-HT2A antagonists Antagonists of the 5-HT2A receptor are sometimes used ...

activity of LSD (~1,000-fold lower in comparison) in the isolated rat

uterus The uterus (from Latin ''uterus'', : uteri or uteruses) or womb () is the hollow organ, organ in the reproductive system of most female mammals, including humans, that accommodates the embryonic development, embryonic and prenatal development, f ...

. In studies 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 ...

and colleagues, iso-LSD fully substituted for LSD in rodent

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. Full substitution occurred at a dose of 0.32mg/kg and its was 0.14mg/kg, whereas the LSD training dose was 0.08mg/kg. Iso-LSD was about 7-fold less potent than LSD in terms of in this assay. In other studies, the drug had about 3.7% of the

toxic Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subst ...

potency of LSD in rabbits (presumably in terms of ) and, unlike LSD, was not pyretogenic.

Pharmacokinetics

Iso-LSD is said to have identical

metabolism Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

to LSD. It has a longer

elimination half-life Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the blood plasma. ...

than LSD. Their half-lives were 12hours and 4.2hours, respectively.

Chemistry

Lysergide stereoisomers structural formulae v

The

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 ...

molecule has two chiral centers at carbons 5 and 8 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 ...

and hence there are four possible

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 ...

s of LSD. Iso-LSD, also known as ''d''-iso-LSD, (+)-iso-LSD, or (5''R''-8''S'')-LSD, is one of four possible stereoisomers. The other isomers are

(''d''-LSD, (+)-LSD, or (5''R'',8''R'')-LSD), ''l''-iso-LSD ((–)-iso-LSD or (5''S'',8''R'')-iso-LSD), and ''l''-LSD ((–)-LSD or (5''S'',8''S'')-LSD). None of them are known to have significant psychoactivity in humans besides LSD. LSD is easily epimerized into iso-LSD with base. Consequently, iso-LSD is a common

synthetic Synthetic may refer to: Science * Synthetic biology * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic elements, chemical elements that are not naturally found on Earth and therefore have to be created in ...

contaminant in

chemical synthesis Chemical synthesis (chemical combination) is the artificial execution of chemical reactions to obtain one or several products. This occurs by physical and chemical manipulations usually involving one or more reactions. In modern laboratory uses ...

of LSD. Iso-LSD can be easily epimerized back into LSD. LSD can degrade into iso-LSD depending on

temperature Temperature is a physical quantity that quantitatively expresses the attribute of hotness or coldness. Temperature is measurement, measured with a thermometer. It reflects the average kinetic energy of the vibrating and colliding atoms making ...

solvent A solvent (from the Latin language, Latin ''wikt:solvo#Latin, solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a Solution (chemistry), solution. A solvent is usually a liquid but can also be a solid, a gas ...

and pH, among other factors. In clinical studies, up to 30% of LSD administered in capsules has been found to isomerize into iso-LSD. Iso-LSD is said to be a

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

of LSD in animals and humans. However, according to other sources, iso-LSD not a metabolite of LSD but is instead only a contaminant.

History

Iso-LSD 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

and colleagues, in the 1940s. The

effects of

were discovered by Hofmann in 1943 when he was using

column chromatography Column chromatography in chemistry is a chromatography method used to isolate a single chemical compounds, chemical compound from a mixture. Chromatography is able to separate substances based on differential absorption of compounds to the adsorbe ...

to separate LSD from iso-LSD that had resulted as an impurity during the

synthesis Synthesis or synthesize may refer to: Science Chemistry and biochemistry *Chemical synthesis, the execution of chemical reactions to form a more complex molecule from chemical precursors **Organic synthesis, the chemical synthesis of organi ...

of LSD.

References

External links

d-iso-LSD - Isomer Design
{{Ergolines Diethylamino compounds Enantiopure drugs Lysergamides Serotonin receptor modulators