Chemistry:LEK-8829
LEK-8829, also known as desoxy-LEK-8842, is a non-selective monoamine receptor modulator of the ergoline family related to the psychedelic drug LSD which has been studied as a potential novel antipsychotic.[1][2][3][4] It is an analogue of LSD in which the oxygen atom of the carboxamide moiety has been removed to instead form an aminomethyl moiety, along with different amine substitutions (methyl and propynyl instead of diethyl).[1][2][3]
The drug acts as a dopamine D1 receptor agonist, dopamine D2 receptor antagonist, and serotonin 5-HT1A and 5-HT2A receptor antagonist, among other actions.[1][2][3] Its affinities for various receptors have been reported, including for the dopamine D1 receptor (Ki = 827 nM), dopamine D2 receptor (Ki = 37 nM), serotonin 5-HT1A receptor (Ki = 3.9 nM), serotonin 5-HT2A receptor (Ki = 5.4 nM), α1-adrenergic receptor (Ki = 245 nM), and α2-adrenergic receptor (Ki = 48 nM), among others.[1][3] However, it may be more potent as a dopamine D1 receptor agonist in vivo.[1][5] LEK-8829 produces effects in animals including hypolocomotion, sedation, catalepsy, antipsychotic-like effects, antiparkinsonian-like effects, slight vasoconstriction, increased or decreased blood pressure, and decreased heart rate.[1][2][3] It dose-dependently inhibits 5-hydroxytryptophan (5-HTP)-induced head twitches.[1][2][3][5][6] The drug also reduces cocaine self-administration and increases striatal opioid peptide levels, but is not self-administered itself.[2][7]
Similarly to LSD, LEK-8829 is sensitive to photodegradation, rapidly decomposing into LEK-1814 (10α-hydroxy-9,10-dihydro-LEK-8829) upon direct exposure to daylight.[1][8] This degradation product was several orders of magnitude less potent than LEK-8829 as a serotonin receptor antagonist.[8] The chemical synthesis of LEK-8829 has been described.[1] Close analogues of LEK-8829 include LEK-8804, LEK-8822, LEK-8841, and LEK-8842 (TRALA-01), among others.[9][10][3] In contrast to LEK-8829, LEK-8804 shows serotonin 5-HT1A receptor agonism[10] and LEK-8842 shows high-efficacy serotonin 5-HT2A receptor partial agonism.[9][11]
LEK-8829 was first described in the scientific literature by 1994.[3] It was developed by the Slovenian pharmaceutical company Lek Pharmaceuticals.[1][2][4] The drug was developed and investigated for potential medical use, including treatment of schizophrenia, other forms of psychosis, parkinsonism, and drug addiction.[1][2][4][12] However, it never progressed beyond the preclinical research stage of development.[4]
See also
- Substituted ergoline
- Substituted lysergamides § Related compounds
- LEK-8842 (oxo-LEK-8829)
- LEK-8822 (9,10-dihydro-LEK-8842)
- LEK-8841 (2-bromo-LEK-8842)
- Romergoline (FCE-23884)
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 "A New Ergoline Derivative, LEK-8829, as a Potential New Antipsychotic Drug". CNS Drug Reviews 2 (3): 294–307. 1996. doi:10.1111/j.1527-3458.1996.tb00303.x. ISSN 1080-563X.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 "Potential applications of dopamine D1 agonist and D2 antagonist LEK-8829.". Slovenski Veterinarski Zbornik 47 (4): 175–180. 2010. https://jeffreydachmd.com/wp-content/uploads/2013/07/Pesticides-as-endocrine-disruptors-Čeh-Katerina-2010.pdf#page=48.
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 "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. October 1994. doi:10.1016/S0022-3565(25)22794-X. PMID 7965734.
- ↑ 4.0 4.1 4.2 4.3 "Delving into the Latest Updates on LEK-8829 with Synapse". 1 November 2025. https://synapse.patsnap.com/drug/cdb21fa9260c48dfa7db6b87e350256c.
- ↑ 5.0 5.1 "The D1 receptor-mediated effects of the ergoline derivative LEK-8829 in rats with unilateral 6-hydroxydopamine lesions". British Journal of Pharmacology 119 (6): 1187–1896. November 1996. doi:10.1111/j.1476-5381.1996.tb16021.x. PMID 8937722.
- ↑ "Modulation of neuroleptic activity of 9,10-didehydro-N-methyl-(2-propynyl)-6-methyl-8-aminomethylergoline bimaleinate (LEK-8829) by D1 intrinsic activity in hemi-parkinsonian rats". Molecular Pharmacology 61 (2): 360–368. February 2002. doi:10.1124/mol.61.2.360. PMID 11809861.
- ↑ "The dopamine D1 receptor agonist and D2 receptor antagonist LEK-8829 attenuates reinstatement of cocaine-seeking in rats". Naunyn-Schmiedeberg's Archives of Pharmacology 369 (6): 576–582. June 2004. doi:10.1007/s00210-004-0937-2. PMID 15138661.
- ↑ 8.0 8.1 "Comparative 5-HT2A-receptor and alpha1-adrenoceptor antagonistic activity of an ergoline LEK-8829 and its degradation product LEK-1814 in rabbit isolated aorta". Pharmacological Research 31: 248. 1995. doi:10.1016/1043-6618(95)87250-7. "LEK-8829 (9,10-didehydro-N-methyl-N-(2-propynyl)-6-methyl-8β-aminomethylergoline), a new potential antipsychotic (Krisch et al., 1994), has been found to be rapidly degraded to 10α-hydroxy-derivative LEK-1814 when exposed to a daylight. [...]".
- ↑ 9.0 9.1 "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. 1992. doi:10.1159/000138998. PMID 1332086.
- ↑ 10.0 10.1 "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. February 1994. doi:10.1016/0091-3057(94)90014-0. PMID 8146221.
- ↑ Trachsel D, Liechti ME, Lustenberger F, "Lysergic acid derivatives with modified LSD-like action", US patent 2023/0414583, published 28 December 2023
- ↑ "Antiparkinsonian potential of interaction of LEK-8829 with bromocriptine". European Journal of Pharmacology 349 (2–3): 151–157. May 1998. doi:10.1016/s0014-2999(98)00287-8. PMID 9671092.
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