RU-24969

RU-24,969 is a serotonin receptor modulator of the tetrahydropyridinylindole group related to 5-MeO-DMT which is used in scientific research.^[1]^[2]^[3]

Other namesRU-24969; RU24969

Drug classSerotonin 5-HT_1B and 5-HT_A receptor agonist

CAS Number

107008-28-6^Y

PubChem CID

108029

Quick facts Clinical data, Other names ...

RU-24969
Clinical data


Other names	RU-24969; RU24969
Drug class	Serotonin 5-HT_1B and 5-HT_A receptor agonist
Identifiers
IUPAC name 5-Methoxy-3-(1,2,5,6-tetrahydro-4-pyridinyl)-1H-indole
CAS Number	107008-28-6^Y
PubChem CID	108029
IUPHAR/BPS	23
ChemSpider	97138^Y
UNII	RKG24J8KJR
CompTox Dashboard (EPA)	DTXSID40276045
Chemical and physical data
Formula	C₁₄H₁₆N₂O
Molar mass	228.295 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES c3cc(OC)cc1c3[nH]cc1C=2CCNCC=2
InChI InChI=1S/C14H16N2O/c1-17-11-2-3-14-12(8-11)13(9-16-14)10-4-6-15-7-5-10/h2-4,8-9,15-16H,5-7H2,1H3^N Key:KRVMLPUDAOWOGN-UHFFFAOYSA-N^N
(verify)

It is a selective agonist of the serotonin 5-HT_1A and 5-HT_1B receptors, with 5-fold preference for the latter receptor over the former.^[1]^[2] In studies, its affinities (K_i) were 2 nM for the serotonin 5-HT₁ receptor, 5 nM for the serotonin 5-HT_1A receptor, 4 nM for the serotonin 5-HT_1B receptor, 780 to 1,000 nM for the serotonin 5-HT₂ receptor, and 400 nM for the serotonin 5-HT_2C receptor.^[4] It also has affinity for the serotonin 5-HT_5A, 5-HT_5B, and 5-HT₇ receptors.^[5]

The drug produces MDMA-like locomotor hyperactivity in animals and this is thought to be mediated by activation of both serotonin 5-HT_1A and 5-HT_1B receptors.^[6]^[1]^[7]^[8]^[9] As with other serotonin 5-HT_1B receptor agonists such as CP-94,253, RU-24,969 has also been found to increase the reinforcing properties of cocaine in animals, suggesting a role for serotonin 5-HT_1B receptors in cocaine addiction as well.^[10] The drug produces antiaggressive effects in rodents.^[11]^[12]^[13]

RU-24,969 was first described in the scientific literature by 1980.^[14]

References

[1]
Martinez-Price D, Krebs-Thomson K, Geyer M (1 January 2002). "Behavioral Psychopharmacology of MDMA and MDMA-Like Drugs: A Review of Human and Animal Studies". Addiction Research & Theory. 10 (1). Informa UK Limited: 43–67. doi:10.1080/16066350290001704. ISSN 1606-6359.
[2]
Doods HN, Kalkman HO, De Jonge A, Thoolen MJ, Wilffert B, Timmermans PB, et al. (June 1985). "Differential selectivities of RU 24969 and 8-OH-DPAT for the purported 5-HT1A and 5-HT1B binding sites. Correlation between 5-HT1A affinity and hypotensive activity". European Journal of Pharmacology. 112 (3): 363–370. doi:10.1016/0014-2999(85)90782-4. PMID 3160596.
[3]
Nichols DE, Oberlender R, McKenna DJ (1991). "Stereochemical Aspects of Hallucinogenesis". In Watson RR (ed.). Biochemistry and Physiology of Substance Abuse. Vol. 3. Boca Raton, Fla.: CRC Press. pp. 1–39. ISBN 978-0-8493-4463-3. OCLC 26748320.
[4]
Glennon RA (January 1987). "Central serotonin receptors as targets for drug research". J Med Chem. 30 (1): 1–12. doi:10.1021/jm00384a001. PMID 3543362. Table II. Affinities of Selected Phenalkylamines for 5-HT1 and 5-HT2 Binding Sites
[5]
Grailhe R, Boschert U, Hen R (1997). "The 5-HT5, 5-HT6 and 5-HT7 receptors". Pharmacochemistry Library. Vol. 27. Elsevier. pp. 311–323. doi:10.1016/s0165-7208(97)80018-9. ISBN 978-0-444-82041-9. ISSN 0165-7208.
[6]
McDougall SA, Robinson JA, Ramirez EL, Diaz HA (February 2020). "Serotonin 5-HT_1A and 5-HT_1B receptors co-mediate the RU 24969-induced locomotor activity of male and female preweanling rats". Pharmacology, Biochemistry, and Behavior. 189 172857. doi:10.1016/j.pbb.2020.172857. PMID 31958472.
[7]
Liechti ME, Vollenweider FX (December 2001). "Which neuroreceptors mediate the subjective effects of MDMA in humans? A summary of mechanistic studies". Human Psychopharmacology. 16 (8): 589–598. doi:10.1002/hup.348. PMID 12404538.
[8]
Rempel NL, Callaway CW, Geyer MA (May 1993). "Serotonin1B receptor activation mimics behavioral effects of presynaptic serotonin release". Neuropsychopharmacology. 8 (3): 201–211. doi:10.1038/npp.1993.22. PMID 8099482.
[9]
Scearce-Levie K, Viswanathan SS, Hen R (January 1999). "Locomotor response to MDMA is attenuated in knockout mice lacking the 5-HT1B receptor". Psychopharmacology. 141 (2): 154–161. doi:10.1007/s002130050819. PMID 9952039.
[10]
Parsons LH, Weiss F, Koob GF (December 1998). "Serotonin1B receptor stimulation enhances cocaine reinforcement". The Journal of Neuroscience. 18 (23): 10078–10089. doi:10.1523/JNEUROSCI.18-23-10078.1998. PMC 6793270. PMID 9822762.
[11]
Olivier B, Mos J (1992). "Rodent models of aggressive behavior and serotonergic drugs". Prog Neuropsychopharmacol Biol Psychiatry. 16 (6): 847–870. doi:10.1016/0278-5846(92)90104-m. PMID 1513929.
[12]
Sánchez C, Arnt J, Hyttel J, Moltzen EK (1993). "The role of serotonergic mechanisms in inhibition of isolation-induced aggression in male mice". Psychopharmacology (Berl). 110 (1–2): 53–59. doi:10.1007/BF02246950. PMID 7870899.
[13]
Olivier B, Mos J, van Oorschot R, Hen R (October 1995). "Serotonin receptors and animal models of aggressive behavior". Pharmacopsychiatry. 28 Suppl 2: 80–90. doi:10.1055/s-2007-979624. PMID 8614705.
[14]
Euvrard C, Boissier JR (April 1980). "Biochemical assessment of the central 5-HT agonist activity of RU 24969 (a piperidinyl indole)". European Journal of Pharmacology. 63 (1): 65–72. doi:10.1016/0014-2999(80)90117-x. PMID 6155275.

See also

References

External links

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