Tochergamine, also known as 621 I.S. or as ''N'',''N''-diethyl-''N''′-(1,2,3,4-tetrahydronaphthyl)glycinamide, is an

oxytocic A uterotonic, also known as an oxytocic or ecbolic, is a type of medication used to induce contraction or greater tonicity of the uterus. Uterotonics are used both to induce labor and to reduce postpartum hemorrhage. Labor induction in the thi ...

drug related to

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 does not appear to have been marketed. It was reported to be effective as an oxytocic agent 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 ...

, with oxytocic activity equivalent to that of ergometrine. In addition, the drug was reported to be effective in

clinical studies Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...

at doses of 2 to 6mg parenterally. However, subsequent research found that it was inactive on the intact human

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 ...

at doses of up to 20mg, and further investigation of tochergamine was abandoned. Tochergamine has a simplified

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 ...

-like

chemical structure A chemical structure of a molecule is a spatial arrangement of its atoms and their chemical bonds. Its determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target m ...

, with a

1-aminotetralin 1-Aminotetralin (1-AT), also known as 1-amino-1,2,3,4-tetrahydronaphthalene, is a chemical compound and one of the possible positional isomers of aminotetralin. It consists of a tetralin core with an amino substituent on one of the carbon atoms. ...

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 is structurally related to lysergamides like ergometrine and

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 ...

. However, it is not technically a partial ergoline or lysergamide, only partial ergoline-like, as its structural features differ in certain regards from those of ergolines and lysergamides. The oxytocic effects of lysergamides like ergometrine are thought to most likely be mediated by

agonism Agonism (from Greek 'struggle') is a political and social theory that emphasizes the potentially positive aspects of certain forms of conflict. It accepts a permanent place for such conflict in the political sphere, but seeks to show how indivi ...

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-HT₂ receptors in

uterine The uterus (from Latin ''uterus'', : uteri or uteruses) or womb () is the organ in the reproductive system of most female mammals, including humans, that accommodates the embryonic and fetal development of one or more fertilized eggs until bir ...

smooth muscle Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called bec ...

tissue. Tochergamine 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 ...

in 1951. It was developed by Daniel Bovet and colleagues at the

Istituto Superiore di Sanità The ''Istituto Superiore di Sanità'' (Italian National Institute of Health, literally 'Higher Health Institute'), also ISS, is an Italian public institution that, as the leading technical-scientific body of the Italian National Health Service ( ...

Rome Rome (Italian language, Italian and , ) is the capital city and most populated (municipality) of Italy. It is also the administrative centre of the Lazio Regions of Italy, region and of the Metropolitan City of Rome. A special named with 2, ...

Italy Italy, officially the Italian Republic, is a country in Southern Europe, Southern and Western Europe, Western Europe. It consists of Italian Peninsula, a peninsula that extends into the Mediterranean Sea, with the Alps on its northern land b ...

. The drug was known as ''tochergamina'' in Italy. It was clinically studied as an oxytocic agent in the 1950s.Bravo, R. R. (1952). Clinical observations on the use of a new synthetic oxytocic drug: N2, N2-diethyl-N1-(1, 2, 3, 4-tetrahydronaphthyl) glycinamide (621 IS). Rend. Ist. Super. Sanita, 15, 1008. https://scholar.google.com/scholar?cluster=5046197701730900775 https://eurekamag.com/research/025/706/025706975.php "The activity of 621 I.S. was observed in 101 cases of normal or surgical birth. The drug is active in doses of 2-6 mg. given either intraven., intramusc, or intra-parietally. Given immediately after parturition it promotes expulsion of the placenta, causing a contraction of the uterus and controlling hemorrhage to within normal limits. Intraven. injn. of 2 mg. produces a prolonged rather than an immediate action and may be used prophylactically. The same dose intraven. is sufficient to obtain good hemostasis, at least in patients without unfavorable conditions (narcosis from ether, for example) in whom doses of 4 and 6 mg. are required. Intraparietal use is particularly important in cesarean section. In 11 cases the uterine reaction occurred in a more than satisfactory manner. In 3 cases in which 6 mg. was given intraven. there was pain in the hypogastric region following intense uterine contraction. The drug has a high margin of tolerance, does not change arterial pressure, and does not produce local effects." Analogues of tochergamine, for instance the

2-aminotetralin 2-Aminotetralin (2-AT), also known as 1,2,3,4-tetrahydronaphthalen-2-amine (THN), is a stimulant drug with a chemical structure consisting of a tetralin core with an amine as substituent. 2-AT is a rigid analogue of phenylisobutylamine and ful ...

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 ...

, have also been described, and have likewise shown oxytocic and

lysergic acid Lysergic acid, also known as -lysergic acid and (+)-lysergic acid, is a precursor for a wide range of ergoline alkaloids that are produced by the ergot fungus and found in the seeds of '' Argyreia nervosa'' ( Hawaiian baby woodrose), and ''Ipomo ...

-like activity.

References

{{Ergolines 1-Aminotetralins Abandoned drugs Carboxamides Diethylamino compounds Partial ergolines Uterotonics

See also

References