Isoergine, also known as isolysergic acid amide (iso-LSA or iso-LA-819), isolysergamide, or erginine, is a

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 ...

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 ...

and

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 ...

families related to

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 ...

(lysergic acid amide; LSA) and

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

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 ergine inverted at the 8 position. Along with ergine and other ergolines, isoergine occurs naturally in morning glories. It is thought to be primarily responsible for the

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 of morning glory seeds.

Use and effects

Isoergine occurs naturally 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 ...

species, including ''

Ipomoea tricolor ''Ipomoea tricolor'', the Mexican morning glory or just morning glory, is a species of flowering plant in the family (biology), family Convolvulaceae, native plant, native to the tropics of the Americas, and widely cultivated and naturalisation ...

'' (tlitliltzin), ''

Ipomoea corymbosa ''Ipomoea corymbosa'' (''Rivea corymbosa'', ''Turbina corymbosa'') is a species of morning glory, native throughout Latin America from Mexico as far south as Peru and widely naturalised elsewhere. Its common names include Christmasvine, Christmas ...

'' (ololiuhqui), and '' Argyreia nervosa'' (Hawaiian baby woodrose). It has been found to constitute 8 to 35% of total

alkaloid Alkaloids are a broad class of natural product, naturally occurring organic compounds that contain at least one nitrogen atom. Some synthetic compounds of similar structure may also be termed alkaloids. Alkaloids are produced by a large varie ...

content relative to 5 to 58% for ergine.

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 ...

, the discoverer of LSD's psychedelic effects, tried 2mg isoergine orally and experienced feelings of unreality, detachment from the outside world, feelings of mental emptiness,

tiredness Fatigue is a state of tiredness (which is not sleepiness), exhaustion or loss of energy. It is a symptom of any of various diseases; it is not a disease in itself. Fatigue (in the medical sense) is sometimes associated with medical conditions ...

, and

apathy Apathy, also referred to as indifference, is a lack of feeling, emotion, interest, or concern about something. It is a state of indifference, or the suppression of emotions such as concern, excitement, motivation, or passion. An apathetic i ...

, though no specific sensory distortions were mentioned. He described its effects as similar to those of ergine, which he had tested at doses of up to 2mg. Subsequently Heim and colleagues assessed ergine at higher doses of 3 to 6mg orally and observed

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 ...

-like effects, while isoergine at 2 to 5mg orally produced notable hallucinogenic effects. The psychedelic effects of isoergine observed in this study included some

euphoria Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and da ...

synaesthesia Synesthesia (American English) or synaesthesia (British English) is a perceptual phenomenon in which stimulation of one sensory or cognitive pathway leads to involuntary experiences in a second sensory or cognitive pathway. People with sy ...

, and altered time perception. However, although hallucinogenic, isoergine's effects were described as not LSD-like. It is thought that ergine and isoergine together may account for most or all of the effects of morning glory seeds, with ergine producing intoxication,

sedation Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Examples of drugs which can be used for sedation include isoflurane, diethyl ether, ...

, and autonomic

side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

s and isoergine producing hallucinogenic effects. Conversely, other notable constituents, including elymoclavine, lysergol, and chanoclavine, produced no

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 ...

or hallucinogenic effects in humans.

Ergometrine Ergonovine, also known as ergometrine and lysergic acid propanolamide, is a medication used to cause contractions of the uterus to treat heavy vaginal bleeding after childbirth. It can be used either by mouth, by injection into a muscle, or ...

, which is a minor constituent representing up to 8% of total alkaloids, is known to produce psychedelic effects only in higher amounts (2–10mg) than those in typical doses of morning glory seeds and hence is thought to not contribute to the effects of the seeds either. Moreover, ergometrine is present in ''Ipomoea tricolor'' and ''Argyreia nervosa'' but not in ''Ipomoea corymbosa''. Isoergine being responsible for the hallucinogenic effects of morning glory seeds is also supported by

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 ...

. However, the poorly-stable lysergic acid hydroxyethylamides (LSHs) might still alternatively be involved in the psychedelic effects of morning glory seeds per

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 ...

Pharmacology

Pharmacodynamics

Isoergine shows

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 labeled with

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, ...

or LSD in rat brain membranes. It has about 10- to 25-fold lower affinity for these receptors than serotonin or LSD and has the same affinity as ergine and iso-LSD ( = 100–200nM for isoergine, 200nM for ergine and iso-LSD, and 8–10nM for LSD). No other

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 ...

interaction data are available for isoergine as of 2020. However, computer-predicted receptor affinities are available for ergine/isoergine (

stereochemistry Stereochemistry, a subdiscipline of chemistry, studies the spatial arrangement of atoms that form the structure of molecules and their manipulation. The study of stereochemistry focuses on the relationships between stereoisomers, which are defined ...

not taken into account). The drug is said to have about 4.3% of LSD's antiserotonergic

potency Potency may refer to: * Potency (pharmacology), a measure of the activity of a drug in a biological system * Virility * Cell potency, a measure of the differentiation potential of stem cells * In homeopathic dilutions, potency is a measure of ho ...

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 ...

''. It is 5- to 33-fold less potent than LSD in producing behavioral changes in the conditioned avoidance test in rodents.

Pharmacokinetics

The

pharmacokinetics Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to describing how the body affects a specific su ...

of isoergine in rodents have been studied. Isoergine is much less

lipophilic Lipophilicity (from Greek language, Greek λίπος "fat" and :wikt:φίλος, φίλος "friendly") is the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such compounds are c ...

than LSD, with log P values of 0.95 and 2.95, respectively. This might influence its

pharmacological Pharmacology is the science of drugs and medications, including a substance's origin, composition, pharmacokinetics, pharmacodynamics, therapeutic use, and toxicology. More specifically, it is the study of the interactions that occur between ...

properties, for instance reducing its

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...

permeability. However, isoergine showed a similar ratio of brain-to-plasma levels as LSD in rodents.

Chemistry

Derivatives

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 isoergine include isolysergic acid diethylamide (iso-LSD), isolysergic acid hydroxyethylamide (iso-LSH), and ergometrinine (isoergometrine; isolysergic acid propanolamide), among others. With the apparent exception of isoergine, isolysergamides, such as iso-LSD, have been found to be inactive as psychedelics in humans.

History

Isoergine was first identified by Sidney Smith and Geoffrey Timmis in 1936 via

hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...

ergot alkaloid 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 ...

s. This followed the identification of ergine in the same way in 1932. Isoergine was first synthesized by

and colleagues by 1949. Subsequently, it was isolated by Hofmann and colleagues in morning glory

seed In botany, a seed is a plant structure containing an embryo and stored nutrients in a protective coat called a ''testa''. More generally, the term "seed" means anything that can be Sowing, sown, which may include seed and husk or tuber. Seeds ...

s in 1960. The

effects of isoergine were first described by Hofmann in 1963. Heim and colleagues more clearly substantiated the hallucinogenic effects of isoergine and its role in producing the psychedelic effects of morning glory seeds in 1968.

References

External links

Isoergine - Isomer Design
{{Serotonin receptor modulators 5-HT2A agonists Alkaloids found in fungi Plant toxins Psychedelic lysergamides Quinoline alkaloids Serotonin receptor modulators Tryptamine alkaloids