Tochergamine

Pharmaceutical compound From Wikipedia, the free encyclopedia

Tochergamine, also known as 621 I.S. or as N,N-diethyl-N′-(1,2,3,4-tetrahydronaphthyl)glycinamide, is an oxytocic drug related to ergometrine which does not appear to have been marketed.^[1]^[2]

Other names621 I.S.; N,N-Diethyl-N′-(1,2,3,4-tetrahydronaphthyl)-glycinamide; Tochergamina

Routes of
administrationParenteral (e.g., intravenous injection, intramuscular injection)

Drug classOxytocic

ATC code

None

Quick facts Clinical data, Other names ...

Tochergamine
Clinical data

Other names	621 I.S.; N,N-Diethyl-N′-(1,2,3,4-tetrahydronaphthyl)-glycinamide; Tochergamina
Routes of administration	Parenteral (e.g., intravenous injection, intramuscular injection)
Drug class	Oxytocic
ATC code	None
Identifiers
IUPAC name N,N-diethyl-2-(1,2,3,4-tetrahydronaphthalen-1-ylamino)acetamide
PubChem CID	43410827
ChemSpider	37924316
Chemical and physical data
Formula	C₁₆H₂₄N₂O
Molar mass	260.381 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES CCN(CC)C(=O)CNC1CCCC2=CC=CC=C12
InChI InChI=1S/C16H24N2O/c1-3-18(4-2)16(19)12-17-15-11-7-9-13-8-5-6-10-14(13)15/h5-6,8,10,15,17H,3-4,7,9,11-12H2,1-2H3 Key:SPTBJOUWQBBDDE-UHFFFAOYSA-N

It was reported to be effective as an oxytocic agent in animal studies, with oxytocic activity equivalent to that of ergometrine.^[3] In addition, the drug was reported to be effective in clinical studies at doses of 2 to 6 mg parenterally.^[2]^[4]^[5] However, subsequent research found that it was inactive on the intact human uterus at doses of up to 20 mg, and further investigation of tochergamine was abandoned.^[3]^[2]

Tochergamine has a simplified lysergamide-like chemical structure, with a 1-aminotetralin ring system, and is structurally related to lysergamides like ergometrine and LSD.^[1]^[6] 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.^[1]^[6] The oxytocic effects of lysergamides like ergometrine are thought to most likely be mediated by agonism of serotonin 5-HT₂ receptors in uterine smooth muscle tissue.^[7]^[8]

Tochergamine was first described in the scientific literature in 1951.^[4] It was developed by Daniel Bovet and colleagues at the Istituto Superiore di Sanità in Rome, Italy.^[2]^[4] The drug was known as tochergamina in Italy.^[4] It was clinically studied as an oxytocic agent in the 1950s.^[2]^[4]^[9]^[5]^[10]

Analogues of tochergamine, for instance the 2-aminotetralin positional isomer, have also been described, and have likewise shown oxytocic and lysergic acid-like activity.^[11]

References

[1]
Campaigne E, Knapp DR (June 1971). "Structural analogs of lysergic acid". Journal of Pharmaceutical Sciences. 60 (6): 809–814. Bibcode:1971JPhmS..60..809C. doi:10.1002/jps.2600600602. PMID 4942861. The tetrahydronaphthylamine derivative (XI) has been used clinically as an oxytocic (21).
[2]
Garrett WJ, Embrey MP (May 1958). "A criterion for oxytocic activity; studies with tochergamine". The Journal of Pharmacy and Pharmacology. 10 (5): 325–327. doi:10.1111/j.2042-7158.1958.tb10309.x. PMID 13539807.
[3]
Embrey MP (January 1962). "The action of drugs on the human uterus: tocograph studies". Postgraduate Medical Journal. 38 (435): 48–54. doi:10.1136/pgmj.38.435.48. PMC 2482488. PMID 13890081. In the case of another new synthetic, 'ergotlike' derivative, tochergamine, our experience was reversed. Found to exhibit oxytocic activity equal to that of ergometrine in experimental animals (Bovet-Nitti, 1952), tochergamine proved quite inactive when tested on the human intact uterus (Garrett and Embrey, 1958).
[4]
Sjostedt S (December 1955). "Tochergamina oder Methergin in der Nachgeburtsperiode?" [Tochergamina and methergin in afterbirth?]. Gynaecologia (in German). 140 (6): 370–374. doi:10.1159/000308104. PMID 13294643. In den letzten Jahren sind in Italien verschiedene Artikel erschie- nen über ein neues synthetisches Präparat mit kräftig uteruskontra- hierender Wirkung. Das Präparat ist von Bovet u. Mitarb. (1951) her- gestellt und am Istituto Superiore di Sanitå in Rom von Bovet-Nitti (1952) synthetisiert und pharmakologisch untersucht worden. Die chemische Bezeichnung ist N,N-diäthyl-N1-(2-tetrahydronaphthyl)- glycinamid-tartrat. Das Präparat trägt in Italien den Namen Tochergamina.
[5]
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."
[6]
Floss HG, Cassady JM, Robbers JE (May 1973). "Influence of ergot alkaloids on pituitary prolactin and prolactin-dependent processes". Journal of Pharmaceutical Sciences. 62 (5): 699–715. Bibcode:1973JPhmS..62..699F. doi:10.1002/jps.2600620502. PMID 4574586. Only a limited amount of information is found in the literature on the relationship between the structure of ergot alkaloids and their activity as nidation inhibitors. Most of this information relates to the peptide-type ergot alkaloids. In early studies, Shelesnyak (81) found little activity for ergotamine (VIa) and its 9,10-dihydro derivative, for ergonovine (Vd) and methylergonovine (lysergic acid butanolamide), for tochergamine, a synthetic analog belonging to the ergotamine group, and for ergocristine (Vle) and its 9,10-dihydro derivative.
[7]
Schiff PL (October 2006). "Ergot and its alkaloids". American Journal of Pharmaceutical Education. 70 (5): 98. doi:10.5688/aj700598 (inactive 1 July 2025). PMC 1637017. PMID 17149427. Ergonovine is a selective and moderately potent tryptaminergic receptor antagonist in various smooth muscles, being only a partially agonistic or antagonistic at tryptaminergic receptors in the central nervous system. In blood vessels the alkaloid is only weakly antagonistic of dopaminergic receptors and partitally agonistic of α-adrenergic receptors. The most pronounced effect of ergonovine is one of direct stimulation of the uterine smooth musculature, resulting in increased muscular tone and an enhancement of the rate and force of rhythmical contractions. This stimulant effect seems to be most closely associated with agonist or partial agonist effects at 5-HT2 receptors. [...] LSD and related hallucinogens are known to interact with brain 5-HT receptors to produce agonist or partial antagonist effects on serotonin activity.{{cite journal}}: CS1 maint: DOI inactive as of July 2025 (link)
[8]
Vallera C, Choi LO, Cha CM, Hong RW (June 2017). "Uterotonic Medications: Oxytocin, Methylergonovine, Carboprost, Misoprostol". Anesthesiology Clinics. 35 (2): 207–219. doi:10.1016/j.anclin.2017.01.007. PMID 28526143. Methylergonovine is a serotonergic receptor agonist in the smooth muscle. It is also a weak antagonist of dopaminergic receptors and partial agonist of α-adrenergic receptors.22 Methylergonovine causes uterine contractions and relaxation at low doses, but causes sustained contractions and increased basal tone at high doses.24 The mechanism of action for uterine contraction is not well defined. Uterine contraction is likely produced by methylergonovine agonist effects on the 5-HT2 receptor found in uterine smooth muscle.22 Alternatively, methylergonovine could cause uterine contraction through direct stimulation of the α-adrenergic receptors in the uterus, which has been postulated to lead to calcium mobilization.25
[9]
Fabiano A (April 1954). "Azione ossitocica di un nuovo prodotto di sintesi, N,N-dietil-N'-(2 tetralil)-glicinammide (tochergamina)" [Oxytocic effect of a new synthetic product, N,N-diethyl-N'-(2-tetraethyl) glycinamide (tochergamine)]. Quaderni di Clinica Ostetrica e Ginecologica (in Italian). 9 (4): 161–172. PMID 13186068.
[10]
Bravo RR (April 1952). "Ensayo clínico del N,N-dietil-N'-(2-tetrahidor 1,2,3,4) naftil glicinamida" [Clinical assay of N,N-diethyl-N'-(2-tetrahydro 1,2,3,4) naphthyl glucinamide]. Boletin. Sociedad Chilena de Obstetricia y Ginecologia (in Spanish). 17 (1): 23–35. PMID 12977883.
[11]
Nichols DE (May 1973). Potential Psychotomimetics: Bromomethoxyamphetamines and Structural Congeners of Lysergic Acid (Thesis). University of Iowa. pp. 27, 41–42. OCLC 1194694085. Marini-Bettolo, Chiavarelli, Bovet, and co-workers (70-80) have tested over 200 derivatives of 1,2,3,4-tetrahydro-2-naphthylamine (2-aminotetralin) 23. This system is analogous to lysergic acid with the B and D rings removed. One of the derivatives 24 bore a striking resemblance to ergonovine and was a potent oxytocic with little vasomotor action (73). From their study of derivatives of 23, Marini-Bettolo, et al,(70) and Bovet, et al,(80) concluded that the 1,2,3,4-tetrahydro-2-naphthylamine element, rather than the indole moiety, in the structure of the ergot alkaloids is essential for sympatholytic activity. [...] Marini-Bettolo and co-workers (70) resolved the 2-aminotetralin derivative 37 and found that the dextro isomer possessed the lysergic acid-like activity. Although the signs of rotation were reported for 36 and 37, the absolute configurations were unknown at that time. More recent studies have shown that the phenylisopropylamines possess the R-(-) and the 2-aminotetralins possess the R-(+) absolute configuration (130, 131). Thus both 36 and 37 have the R configuration and correlate with lysergic acid. Although these agents have arisen from a search for better oxytocic agents, one may speculate that they reflect the action of the lysergic acid nucleus itself.

Tochergamine

See also

References

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