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| 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 |
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| ChemSpider | |
| Chemical and physical data | |
| Formula | C16H24N2O |
| Molar mass | 260.381 g·mol−1 |
| 3D model (JSmol) | |
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Tochergamine, also known as621 I.S. or asN,N-diethyl-N′-(1,2,3,4-tetrahydronaphthyl)glycinamide, is anoxytocic drug related toergometrine which does not appear to have been marketed.[1][2]
It was reported to be effective as an oxytocic agent inanimal studies, with oxytocic activity equivalent to that of ergometrine.[3] In addition, the drug was reported to be effective inclinical studies at doses of 2 to 6 mgparenterally.[2][4][5] However, subsequent research found that it was inactive on the intact humanuterus at doses of up to 20 mg, and further investigation of tochergamine was abandoned.[3][2]
Tochergamine has a simplifiedlysergamide-likechemical structure, with a1-aminotetralinring system, and isstructurally related to lysergamides like ergometrine andLSD.[1][6] However, it is not technically apartial 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 byagonism ofserotonin5-HT2 receptors inuterinesmooth muscletissue.[7][8]
Tochergamine was first described in thescientific literature in 1951.[4] It was developed by Daniel Bovet and colleagues at theIstituto Superiore di Sanità inRome,Italy.[2][4] The drug was known astochergamina in Italy.[4] It was clinically studied as an oxytocic agent in the 1950s.[2][4][9][5][10]
Analogues of tochergamine, for instance the2-aminotetralinpositional isomer, have also been described, and have likewise shown oxytocic andlysergic acid-like activity.[11]
The tetrahydronaphthylamine derivative (XI) has been used clinically as an oxytocic (21).
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).
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.
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.
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)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
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.