LEK-8804

LEK-8804
Clinical data
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-HT1A receptor agonist; Serotonin 5-HT2A receptor antagonist
ATC code
  • None
Identifiers
  • (6aR,9R)-7-methyl-N-prop-2-ynyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide
CAS Number
PubChem CID
ChemSpider
ChEMBL
Chemical and physical data
FormulaC19H19N3O
Molar mass305.381 g·mol−1
3D model (JSmol)
  • CN1C[C@@H](C=C2[C@H]1CC3=CNC4=CC=CC2=C34)C(=O)NCC#C
  • 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

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]

The drug shows affinity for the serotonin 5-HT1A, 5-HT2A, and 5-HT2C receptors (Ki = 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-HT1A receptor full agonist and serotonin 5-HT2A receptor antagonist.[1] For instance, it fully substitutes for the serotonin 5-HT1A receptor agonist 8-OH-DPAT in rodent drug discrimination tests and produces other serotonin 5-HT1A receptor agonist-like behavioral effects.[1][3] The drug does not induce the head-twitch response, a behavioral proxy of serotonin 5-HT2A 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-HT1A receptor agonist without significant serotonin 5-HT2A 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]

See also

References

  1. ^ a b c d e f g h i j 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.
  2. ^ Kleven MS, Koek W (February 1996). "Pharmacological characterization of in vivo properties of putative mixed 5-HT1A agonist/5-HT2A/2C antagonist anxiolytics. I. Antipunishment effects in the pigeon". The Journal of Pharmacology and Experimental Therapeutics. 276 (2): 388–397. doi:10.1016/S0022-3565(25)12286-6. PMID 8632301.
  3. ^ a b c d e f g Kleven MS, Assié MB, Koek W (August 1997). "Pharmacological characterization of in vivo properties of putative mixed 5-HT1A agonist/5-HT(2A/2C) antagonist anxiolytics. II. Drug discrimination and behavioral observation studies in rats". The Journal of Pharmacology and Experimental Therapeutics. 282 (2): 747–759. doi:10.1016/S0022-3565(24)36843-0. PMID 9262338.
  4. ^ Kleven MS, Koek W (January 1998). "Discriminative stimulus effects of 8-hydroxy-2-(di-n-propylamino)tetralin in pigeons and rats: species similarities and differences". The Journal of Pharmacology and Experimental Therapeutics. 284 (1): 238–249. doi:10.1016/S0022-3565(24)37196-4. PMID 9435184.
  5. ^ 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.
  6. ^ 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.
  7. ^ Krisch I, Rucman R, Lavric A, Ocvirk M, Bole-Vunduk B (1996). "A New Ergoline Derivative, LEK-8829, as a Potential New Antipsychotic Drug". CNS Drug Reviews. 2 (3): 294–307. doi:10.1111/j.1527-3458.1996.tb00303.x. ISSN 1080-563X.
  8. ^ Zivin M, Sprah L, Sket D (November 1996). "The D1 receptor-mediated effects of the ergoline derivative LEK-8829 in rats with unilateral 6-hydroxydopamine lesions". British Journal of Pharmacology. 119 (6): 1187–1196. doi:10.1111/j.1476-5381.1996.tb16021.x. PMC 1915887. PMID 8937722.
  9. ^ Zivin M, Sprah L, Sket D (May 1998). "Antiparkinsonian potential of interaction of LEK-8829 with bromocriptine". European Journal of Pharmacology. 349 (2–3): 151–157. doi:10.1016/s0014-2999(98)00287-8. PMID 9671092.
  10. ^ Glavan G, Sket D, Zivin M (February 2002). "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. doi:10.1124/mol.61.2.360. PMID 11809861.
  11. ^ Živin M (2010). "Potential applications of dopamine D1 agonist and D2 antagonist LEK-8829" (PDF). Slovenski Veterinarski Zbornik [Slovenian Veterinary Research]. 47 (4): 175–180.
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