Chemistry:LEK-8804

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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

  • Substituted lysergamide
  • LEK-8842, LEK-8822, LEK-8829, LEK-8841

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 "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. 
  2. ↑ "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. February 1996. doi:10.1016/S0022-3565(25)12286-6. PMID 8632301. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 "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. August 1997. doi:10.1016/S0022-3565(24)36843-0. PMID 9262338. 
  4. ↑ "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. January 1998. doi:10.1016/S0022-3565(24)37196-4. PMID 9435184. 
  5. ↑ "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. 
  6. ↑ "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. 
  7. ↑ "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. 
  8. ↑ "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. November 1996. doi:10.1111/j.1476-5381.1996.tb16021.x. PMID 8937722. 
  9. ↑ "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. 
  10. ↑ "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. 
  11. ↑ "Potential applications of dopamine D1 agonist and D2 antagonist LEK-8829.". Slovenski Veterinarski Zbornik 47 (4): 175–180. 2010. https://www.academia.edu/download/48241398/POTENTIAL_APPLICATIONS_OF_DOPAMINE_D1_AG20160822-5721-68vojm.pdf. 



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