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Pharmaceutical compound
LEK-8842
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Clinical data
Other namesLEK8842; TRALA-01; TRALA01; N-Methyl-N-(2-propynyl)lysergamide; 9,10-Didehydro-N-methyl-N-(2-propynyl)-6-methylergoline-8β-carboxamide; "Compound 2a"
Drug classSerotonin receptor modulator; Serotonin 5-HT2A receptor agonist
ATC code
  • None
Identifiers
  • (6aR,9R)-N,7-dimethyl-N-prop-2-ynyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide
PubChem CID
ChemSpider
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC20H21N3O
Molar mass319.408 g·mol−1
3D model (JSmol)
  • CN1C[C@@H](C=C2[C@H]1CC3=CNC4=CC=CC2=C34)C(=O)N(C)CC#C
  • InChI=1S/C20H21N3O/c1-4-8-22(2)20(24)14-9-16-15-6-5-7-17-19(15)13(11-21-17)10-18(16)23(3)12-14/h1,5-7,9,11,14,18,21H,8,10,12H2,2-3H3/t14-,18-/m1/s1
  • Key:NTIBYWGZNANJNM-RDTXWAMCSA-N

LEK-8842, also known as N-methyl-N-(2-propynyl)lysergamide or as TRALA-01, is a serotonin receptor modulator of the lysergamide family related to the psychedelic drug LSD.[1][2][3]

The drug is described as showing serotonin 5-HT2 receptor partial agonistic activity and α-adrenergic receptor agonistic activity based on in-vitro tissue assays that included selective antagonist challenges.[1][2] Subsequently, it was found to be a potent partial agonist of the serotonin 5-HT2A and 5-HT2B receptors and to show affinity for the serotonin 5-HT2C receptor.[3] LEK-8842 produces effects in animals including serotonin behavioral syndrome, hyperthermia, pressor effects, pupil dilation, and uterine contractions.[2]

The chemical synthesis of LEK-8842 has been described.[3] Several analogues of LEK-8842 have been described, for instance LEK-8804 (N-(2-propynyl)lysergamide) among others.[2][4][5]

LEK-8842 was first described in the scientific literature by 1992.[2] It was developed by the Slovenian pharmaceutical company LEK Pharmaceuticals.[2] Subsequently, LEK-8842 was studied and patented by Matthias Liechti and Daniel Trachsel and colleagues in association with Mind Medicine (Definium Therapeutics) in 2023.[3]

See also

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References

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  1. ^ a b Fornai F, Ruffoli R, Soldani P, Ruggieri S, Paparelli A (2007). "The "Parkinsonian heart": from novel vistas to advanced therapeutic approaches in Parkinson's disease". Current Medicinal Chemistry. 14 (23): 2421–2428. doi:10.2174/092986707782023631. PMID 17979697. Structure-activity studies on ergot derivatives, based on substitution of the ergoline nucleus, demonstrated that hydrogenation of the double bond in the position 9,10 of the nucleus of the derivative attenuates the potency and the intrinsic activity on alpha adrenoceptors. In particular, in the study of Krisch et al. [95] the authors used a sample ergot structure named 9,10-didehydro-Nmethyl-N-(2-propynyl)-6-methylergoline-8 beta-carboxamide (LEK 8842). They observed that this ergot compound possesses mild 5HT2 and strong alpha-adrenergic activity. The hydrogenation of the 9-10 bound erased the 5HT activity while reduce significantly the activity at alpha receptors up to a point that in the presence of high agonist concentration its effect is turned into an antagonism at alpha adrenoceptors.
  2. ^ a b c d e f Krisch I, Budihna MV, Rucman R (1992). "Structure-activity study of some newly synthesized ergoline derivatives on 5-HT2 receptors and alpha-adrenoceptors in rabbit isolated aorta". Pharmacology. 45 (4): 195–208. doi:10.1159/000138998. PMID 1332086.
  3. ^ a b c d 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.
  4. ^ Krisch I, Bole-Vunduk B (February 1994). "Behavioral studies on LEK-8804, a new ergoline derivative with potent 5-HT1A receptor agonist and 5-HT2 receptor antagonist activity". Pharmacology, Biochemistry, and Behavior. 47 (2): 301–305. doi:10.1016/0091-3057(94)90014-0. PMID 8146221.
  5. ^ Krisch I, Bole-Vunduk B, Pepelnak M, Lavric B, Ocvirk A, Budihna MV, et al. (October 1994). "Pharmacological studies with two new ergoline derivatives, the potential antipsychotics LEK-8829 and LEK-8841". The Journal of Pharmacology and Experimental Therapeutics. 271 (1): 343–352. doi:10.1016/S0022-3565(25)22794-X. PMID 7965734.

External links

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5-HT1
5-HT1A
  • Positive allosteric modulators: Oleamide
5-HT1B
  • Miscellaneous: HG1 (5-HT-moduline antagonist)
5-HT1D
5-HT1E
5-HT1F
5-HT2
5-HT2A
5-HT2B
5-HT2C
5-HT3–7
5-HT3
5-HT4
5-HT5A
5-HT6
5-HT7
  • Negative allosteric modulators: Oleamide
α1
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Antagonists
α2
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Antagonists
β
Agonists
Antagonists
Ergolines
(incl. lysergines)
Clavines
(6,8-dimethylergolines)
Lysergamides
(lysergic acid amides)
Ergopeptines
(peptide ergolines)
Partial ergolines
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