LEK-8829
Pharmaceutical compound
From Wikipedia, the free encyclopedia
LEK-8829 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]
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| Other names | LEK8829; LEK-882; LEK882; 9,10-Didehydro-N-methyl-N-(2-propynyl)-6-methyl-8β-aminomethylergoline |
| Drug class | Non-selective monoamine receptor modulator; Dopamine D1 receptor agonist; Dopamine D2 receptor antagonist; Serotonin 5-HT1A receptor antagonist; Serotonin 5-HT2A receptor antagonist |
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| Formula | C20H23N3 |
| Molar mass | 305.425 g·mol−1 |
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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]