TRALA-12

TRALA-12
Clinical data
Other names	TRALA12; N-Ethenyl-N-ethyllysergamide; N-Vinyl-N-ethyllysergamide; Lysergic acid ethenylethylamide; Lysergic acid vinylethylamide; N-Ethenyl-N-ethyl-6-methyl-9,10-didehydroergoline-8β-carboxamide; "Compound 2l"
Routes of; administration	Oral or intravenous
Drug class	Serotonin receptor modulator; Serotonin 5-HT2 receptor agonist; Serotonin 5-HT2A receptor agonist; Possible serotonergic psychedelic or hallucinogen
ATC code	None;
Identifiers
	IUPAC name (6aR,9R)-N-ethenyl-N-ethyl-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide;
CAS Number	65527-59-5;
PubChem CID	54085403;
ChemSpider	62838598;
Chemical and physical data
Formula	C20H23N3O
Molar mass	321.424 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CCN(C=C)C(=O)[C@H]1CN([C@@H]2CC3=CNC4=CC=CC(=C34)C2=C1)C;
	InChI InChI=1S/C20H23N3O/c1-4-23(5-2)20(24)14-9-16-15-7-6-8-17-19(15)13(11-21-17)10-18(16)22(3)12-14/h4,6-9,11,14,18,21H,1,5,10,12H2,2-3H3/t14-,18-/m1/s1; Key:MQCCUHBPZPBYDB-RDTXWAMCSA-N;

TRALA-12, also known as N-ethenyl-N-ethyllysergamide or as lysergic acid vinylethylamide, is a serotonin receptor modulator and possible psychedelic drug of the lysergamide family related to lysergic acid diethylamide (LSD).^[1] It is the analogue of LSD in which one of the ethyl groups on the amide has been replaced with an ethenyl (vinyl) group.^[1] Didehydro-LSD (DDH-LSD), which is structurally and pharmacologically compatible with TRALA-12, is being developed by Matthias Liechti and colleagues as a shorter-lasting LSD analogue for potential medical use.^[2]

Pharmacology

Pharmacodynamics

TRALA-12 is a potent agonist of the serotonin 5-HT₂ receptors similarly to LSD.^[1] Its affinities (K_i) were 0.09 nM for the serotonin 5-HT_2A receptor, 0.67 nM for the serotonin 5-HT_2B receptor, and 3.8 nM for the serotonin 5-HT_2C receptor.^[1] Conversely, its activational potencies and efficacies (EC₅₀Tooltip half-maximal effective concentration (E_maxTooltip maximal efficacy)) were 0.93 nM (79%) at the serotonin 5-HT_2A receptor and 1.7 nM (42%) at the serotonin 5-HT_2B receptor, whereas values for the serotonin 5-HT_2C receptor were not reported.^[1] TRALA-12 showed 19-fold higher affinity for the serotonin 5-HT_2A receptor than LSD, though it had only 1.5-fold higher activational potency at the receptor and had slightly lower efficacy (E_max = 79% and 90%, respectively).^[1] It similarly showed greatly increased affinities for the serotonin 5-HT_2B and 5-HT_2C receptors compared to LSD.^[1]

Pharmacokinetics

TRALA-12 shows dramatically faster metabolism than LSD in human liver microsomes in vitro.^[1] Whereas about 75% remained in the case of LSD following incubation after 4 hours, only about 10% of TRALA-12 remained with incubation after 1 hour.^[1] It was concluded that due to its very fast metabolism, TRALA-12 is likely not orally active, but may be active via intravenous infusion with short-lasting effects that can be rapidly terminated upon cessation of infusion.^[1]

Chemistry

Synthesis

The chemical synthesis of TRALA-12 has been described.^[1]

History

TRALA-12 was patented by Daniel Trachsel and Matthias Liechti and colleagues in association with MindMed (Mind Medicine; now Definium Therapeutics) in 2023.^[1]

Research

An LSD analogue called didehydro-LSD (DDH-LSD), which has a name that is structurally compatible with TRALA-12, is being developed by Matthias Liechti and colleagues as a potential novel psychedelic drug for medical applications.^[2] It is described as having similar receptor activity as LSD in vitro but as having faster in-vitro metabolism and hence as potentially having a shorter duration in comparison, similarly to the case of TRALA-12.^[2] A pharmacokinetic clinical study of DDH-LSD comparing it with LSD is underway at University Hospital Basel in Basel, Switzerland as of March 2026, with both drugs given orally (following an initial dose-finding substudy in the case of DDH-LSD).^[2]

References

1 2 3 4 5 6 7 8 9 10 11 12 13 US 2023/0414583, Trachsel D, Liechti ME, Lustenberger F, "Lysergic acid derivatives with modified LSD-like action", published 28 December 2023, assigned to Mind Medicine Inc.
1 2 3 4 5 "Pharmacokinetics of Didehydro-LSD (DDH-LSD) Compared With LSD (DDH-LSD)". ClinicalTrials.gov. 9 March 2026. Retrieved 15 April 2026.

External links

TRALA-12 - Isomer Design

[US20230414583A1-1] 1 2 3 4 5 6 7 8 9 10 11 12 13 US 2023/0414583, Trachsel D, Liechti ME, Lustenberger F, "Lysergic acid derivatives with modified LSD-like action", published 28 December 2023, assigned to Mind Medicine Inc.

[NCT07309471-2] 1 2 3 4 5 "Pharmacokinetics of Didehydro-LSD (DDH-LSD) Compared With LSD (DDH-LSD)". ClinicalTrials.gov. 9 March 2026. Retrieved 15 April 2026.

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