LEK-8804

LEK-8804, also known as N-(2-propynyl)lysergamide, is a serotonin receptor modulator of the lysergamide family related to the psychedelic drug LSD.^[1][2][3][4] It is the derivative of ergine (lysergic acid amide; LSA) with an N-(2-propynyl) substitution on the carboxamide moiety.^[1]

Other namesLEK8804; 9,10-Didehydro-N-(2-propynyl)-6-methylergoline-8β-carboxamide; N-(2-Propynyl)ergine; N-(2-Propynyl)lysergamide

Drug classSerotonin receptor modulator; Serotonin 5-HT_1A receptor agonist; Serotonin 5-HT_2A receptor antagonist

ATC code

• None

CAS Number

• 153415-44-2

Quick facts Clinical data, Other names ...

LEK-8804

Clinical data
Other names	LEK8804; 9,10-Didehydro-N-(2-propynyl)-6-methylergoline-8β-carboxamide; N-(2-Propynyl)ergine; N-(2-Propynyl)lysergamide
Drug class	Serotonin receptor modulator; Serotonin 5-HT1A receptor agonist; Serotonin 5-HT2A receptor antagonist
ATC code	None
Identifiers
IUPAC name (6aR,9R)-7-methyl-N-prop-2-ynyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide
CAS Number	153415-44-2
PubChem CID	11779864
ChemSpider	9954546
ChEMBL	ChEMBL5618531
CompTox Dashboard (EPA)	DTXSID20165322
Chemical and physical data
Formula	C19H19N3O
Molar mass	305.381 g·mol−1
3D model (JSmol)	Interactive image
SMILES CN1C[C@@H](C=C2[C@H]1CC3=CNC4=CC=CC2=C34)C(=O)NCC#C
InChI InChI=1S/C19H19N3O/c1-3-7-20-19(23)13-8-15-14-5-4-6-16-18(14)12(10-21-16)9-17(15)22(2)11-13/h1,4-6,8,10,13,17,21H,7,9,11H2,2H3,(H,20,23)/t13-,17-/m1/s1 Key:WZTGESDWBWZMSE-CXAGYDPISA-N

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The drug shows affinity for the serotonin 5-HT_1A, 5-HT_2A, and 5-HT_2C receptors (K_i = 0.56–0.6 nM, 15–60 nM, and 10–80 nM, respectively).^[1][3] It also shows weaker affinity for dopamine and adrenergic receptors.^[1][3] Based on animal behavioral studies, it is thought that LEK-8804 may act as a potent serotonin 5-HT_1A receptor full agonist and serotonin 5-HT_2A receptor antagonist.^[1] For instance, it fully substitutes for the serotonin 5-HT_1A receptor agonist 8-OH-DPAT in rodent drug discrimination tests and produces other serotonin 5-HT_1A receptor agonist-like behavioral effects.^[1][3] The drug does not induce the head-twitch response, a behavioral proxy of serotonin 5-HT_2A receptor activation and psychedelic effects, in rodents.^[1] Instead, it dose-dependently inhibits 5-hydroxytryptophan (5-HTP)- and DOI-induced head twitches.^[1][3] On the other hand, LEK-8804 failed to substantially block the discriminative stimulus effects of DOI in rodent drug discrimination tests.^[3] These findings suggest that LEK-8804 may actually be acting merely as a serotonin 5-HT_1A receptor agonist without significant serotonin 5-HT_2A receptor antagonism.^[3]

Close analogues of LEK-8804 include LEK-8842, LEK-8829, and LEK-8841, among others.^{[5][6][7][8][9][10][11]}

LEK-8804 was first described in the scientific literature by 1994.^[1] It was developed by the Slovenian pharmaceutical company LEK Pharmaceuticals.^[1]