8-OH-DPAT

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8-OH-DPAT
8-OH-DPAT chemical structure.svg
8-OH-DPAT 3D.png
Clinical data
Other names8-Hydroxy-2-(dipropylamino)tetralin; 8-Hydroxy-2-(di-n-propylamino)tetralin
Drug class Serotonin 5-HT1A receptor agonist; Serotonin 5-HT7 receptor agonist; Serotonin reuptake inhibitor or releasing agent
ATC code
  • None
Identifiers
  • 7-(dipropylamino)-5,6,7,8-tetrahydronaphthalen-1-ol
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C16H25NO
Molar mass 247.382 g·mol−1
3D model (JSmol)
  • CCCN(CCC)C1CCc2cccc(O)c2C1
  • InChI=1S/C16H25NO/c1-3-10-17(11-4-2)14-9-8-13-6-5-7-16(18)15(13)12-14/h5-7,14,18H,3-4,8-12H2,1-2H3 Yes check.svgY
  • Key:ASXGJMSKWNBENU-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

8-OH-DPAT, also known as 8-hydroxy-2-(dipropylamino)tetralin, is a serotonin 5-HT1A receptor agonist of the 2-aminotetralin family which was developed in the 1980s and has been widely used to study the function of the 5-HT1A receptor. [1] [2] It was one of the first major 5-HT1A receptor full agonists to have been discovered.

Contents

Originally believed to be selective for the 5-HT1A receptor, 8-OH-DPAT was later found to act as a serotonin 5-HT7 receptor agonist and serotonin reuptake inhibitor or releasing agent as well. [3] [4] [5] [6] [7]

In animal studies, 8-OH-DPAT has been shown to possess antidepressant, [8] anxiolytic, [9] prosocial, [10] [11] serenic (antiaggressive), [12] [11] prosexual, [13] anorectic, [14] antiemetic, [15] hypothermic, [16] hypotensive, [17] bradycardic, [17] hyperventilative, [18] [19] [20] and analgesic effects. [21]

8-OH-DPAT dose-dependently increases oxytocin levels in rodents. [22] [23] [24] [25] [26] [27] [28] It can also strongly increase oxytocin gene expression in monkeys. [29] Continuous administration of the selective serotonin reuptake inhibitor (SSRI) fluoxetine or serotonin transporter (SERT) knockout can blunt the increased oxytocin levels with 8-OH-DPAT in rodents via desensitization of postsynaptic serotonin 5-HT1A receptors. [30] [31] [32] [33] The increase in oxytocin levels with 8-OH-DPAT is mediated by activation of the Gz pathway of the serotonin 5-HT1A receptor. [34] [35] [30] The prosocial effects of 8-OH-DPAT in rodents can be blocked by oxytocin receptor antagonists tocinoic acid and L-368,899. [10] [11] In addition, the prosexual effects of 8-OH-DPAT in rodents can be moderately antagonized by the oxytocin receptor antagonist OXTR-A. [13] Conversely, the oxytocin receptor antagonist L-368,899 had no effect on the antiaggressive effects of 8-OH-DPAT. [11]

See also

References

  1. ↑ Glennon RA (1992). "Concepts for the design of 5-HT 1A serotonin agonists and antagonists" . Drug Development Research. 26 (3): 251–274. doi:10.1002/ddr.430260306. ISSN   0272-4391 . Retrieved 19 November 2025.
  2. ↑ Shulgin A, Manning T, Daley P (2011). The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds . Vol. 1. Berkeley: Transform Press. ISBN   978-0-9630096-3-0.
  3. ↑ Larsson LG, Rényi L, Ross SB, Svensson B, Angeby-Möller K (February 1990). "Different effects on the responses of functional pre- and postsynaptic 5-HT1A receptors by repeated treatment of rats with the 5-HT1A receptor agonist 8-OH-DPAT". Neuropharmacology. 29 (2): 85–91. doi:10.1016/0028-3908(90)90047-U. PMID   1691832. S2CID   39066002.
  4. ↑ Sprouse J, Reynolds L, Li X, Braselton J, Schmidt A (January 2004). "8-OH-DPAT as a 5-HT7 agonist: phase shifts of the circadian biological clock through increases in cAMP production". Neuropharmacology. 46 (1): 52–62. doi:10.1016/j.neuropharm.2003.08.007. PMID   14654097. S2CID   41623573.
  5. ↑ "IUPHAR DATABASE - 5-Hydroxytryptamine receptors - 5-HT7". Archived from the original on 2016-03-03. Retrieved 2009-09-23.
  6. ↑ Assié MB, Koek W (November 1996). "Possible in vivo 5-HT reuptake blocking properties of 8-OH-DPAT assessed by measuring hippocampal extracellular 5-HT using microdialysis in rats". British Journal of Pharmacology. 119 (5): 845–850. doi:10.1111/j.1476-5381.1996.tb15749.x. PMC   1915946 . PMID   8922730.
  7. ↑ Wölfel R, Graefe KH (February 1992). "Evidence for various tryptamines and related compounds acting as substrates of the platelet 5-hydroxytryptamine transporter". Naunyn-Schmiedeberg's Archives of Pharmacology. 345 (2): 129–136. doi:10.1007/BF00165727. PMID   1570019. S2CID   2984583.
  8. ↑ Luscombe GP, Martin KF, Hutchins LJ, Gosden J, Heal DJ (March 1993). "Mediation of the antidepressant-like effect of 8-OH-DPAT in mice by postsynaptic 5-HT1A receptors". British Journal of Pharmacology. 108 (3): 669–677. doi:10.1111/j.1476-5381.1993.tb12859.x. PMC   1908013 . PMID   8467355.
  9. ↑ Schreiber R, De Vry J (November 1993). "Neuronal circuits involved in the anxiolytic effects of the 5-HT1A receptor agonists 8-OH-DPAT ipsapirone and buspirone in the rat". European Journal of Pharmacology. 249 (3): 341–351. doi:10.1016/0014-2999(93)90531-L. PMID   7904566.
  10. 1 2 Thompson MR, Callaghan PD, Hunt GE, Cornish JL, McGregor IS (May 2007). "A role for oxytocin and 5-HT(1A) receptors in the prosocial effects of 3,4 methylenedioxymethamphetamine ("ecstasy")". Neuroscience. 146 (2): 509–514. doi:10.1016/j.neuroscience.2007.02.032. PMID   17383105.
  11. 1 2 3 4 Tan O, Martin LJ, Bowen MT (July 2020). "Divergent pathways mediate 5-HT1A receptor agonist effects on close social interaction, grooming and aggressive behaviour in mice: Exploring the involvement of the oxytocin and vasopressin systems". J Psychopharmacol. 34 (7): 795–805. doi:10.1177/0269881120913150. PMID   32312154.
  12. ↑ de Boer SF, Koolhaas JM (December 2005). "5-HT1A and 5-HT1B receptor agonists and aggression: a pharmacological challenge of the serotonin deficiency hypothesis". European Journal of Pharmacology. 526 (1–3): 125–139. doi:10.1016/j.ejphar.2005.09.065. PMID   16310183.
  13. 1 2 de Jong TR, Neumann ID (January 2015). "Moderate role of oxytocin in the pro-ejaculatory effect of the 5-HT1A receptor agonist 8-OH-DPAT". J Sex Med. 12 (1): 17–28. doi:10.1111/jsm.12742. PMID   25359190.
  14. ↑ Dourish CT, Hutson PH, Curzon G (October 1985). "Characteristics of feeding induced by the serotonin agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT)". Brain Research Bulletin. 15 (4): 377–384. doi:10.1016/0361-9230(85)90005-X. PMID   2933126. S2CID   11047288.
  15. ↑ Lucot JB (February 1994). "Antiemetic effects of flesinoxan in cats: comparisons with 8-hydroxy-2-(di-n-propylamino)tetralin". European Journal of Pharmacology. 253 (1–2): 53–60. doi:10.1016/0014-2999(94)90756-0. PMID   8013549.
  16. ↑ O'Connell MT, Sarna GS, Curzon G (July 1992). "Evidence for postsynaptic mediation of the hypothermic effect of 5-HT1A receptor activation". British Journal of Pharmacology. 106 (3): 603–609. doi:10.1111/j.1476-5381.1992.tb14382.x. PMC   1907559 . PMID   1387027.
  17. 1 2 Fozard JR, Mir AK, Middlemiss DN (March 1987). "Cardiovascular response to 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in the rat: site of action and pharmacological analysis". Journal of Cardiovascular Pharmacology. 9 (3): 328–347. doi: 10.1097/00005344-198703000-00010 . PMID   2437400. S2CID   24327371.
  18. ↑ Sahibzada N, Ferreira M, Wasserman AM, Taveira-DaSilva AM, Gillis RA (February 2000). "Reversal of morphine-induced apnea in the anesthetized rat by drugs that activate 5-hydroxytryptamine(1A) receptors". The Journal of Pharmacology and Experimental Therapeutics. 292 (2): 704–713. doi:10.1016/S0022-3565(24)35342-X. PMID   10640309.
  19. ↑ Meyer LC, Fuller A, Mitchell D (February 2006). "Zacopride and 8-OH-DPAT reverse opioid-induced respiratory depression and hypoxia but not catatonic immobilization in goats". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 290 (2): R405–R413. doi:10.1152/ajpregu.00440.2005. PMID   16166206. S2CID   224414.
  20. ↑ Guenther U, Manzke T, Wrigge H, Dutschmann M, Zinserling J, Putensen C, et al. (April 2009). "The counteraction of opioid-induced ventilatory depression by the serotonin 1A-agonist 8-OH-DPAT does not antagonize antinociception in rats in situ and in vivo". Anesthesia and Analgesia. 108 (4): 1169–1176. doi: 10.1213/ane.0b013e318198f828 . PMID   19299781. S2CID   25951835.
  21. ↑ Xu W, Qiu XC, Han JS (June 1994). "Serotonin receptor subtypes in spinal antinociception in the rat". The Journal of Pharmacology and Experimental Therapeutics. 269 (3): 1182–1189. doi:10.1016/S0022-3565(25)38857-9. PMID   8014862. Archived from the original on 2020-01-25. Retrieved 2009-07-10.
  22. ↑ Bagdy G, Kalogeras KT (May 1993). "Stimulation of 5-HT1A and 5-HT2/5-HT1C receptors induce oxytocin release in the male rat". Brain Res. 611 (2): 330–332. doi:10.1016/0006-8993(93)90521-n. PMID   8334526.
  23. ↑ Li Q, Levy AD, Cabrera TM, Brownfield MS, Battaglia G, Van de Kar LD (December 1993). "Long-term fluoxetine, but not desipramine, inhibits the ACTH and oxytocin responses to the 5-HT1A agonist, 8-OH-DPAT, in male rats". Brain Res. 630 (1–2): 148–156. doi:10.1016/0006-8993(93)90652-4. PMID   8118681.
  24. ↑ Uvnäs-Moberg K, Hillegaart V, Alster P, Ahlenius S (1996). "Effects of 5-HT agonists, selective for different receptor subtypes, on oxytocin, CCK, gastrin and somatostatin plasma levels in the rat". Neuropharmacology. 35 (11): 1635–1640. doi:10.1016/s0028-3908(96)00078-0. PMID   9025112.
  25. ↑ Li Q, Muma NA, van de Kar LD (November 1996). "Chronic fluoxetine induces a gradual desensitization of 5-HT1A receptors: reductions in hypothalamic and midbrain Gi and G(o) proteins and in neuroendocrine responses to a 5-HT1A agonist". J Pharmacol Exp Ther. 279 (2): 1035–1042. PMID   8930214.
  26. ↑ Vicentic A, Li Q, Battaglia G, Van de Kar LD (April 1998). "WAY-100635 inhibits 8-OH-DPAT-stimulated oxytocin, ACTH and corticosterone, but not prolactin secretion". Eur J Pharmacol. 346 (2–3): 261–266. doi:10.1016/s0014-2999(97)01607-5. PMID   9652368.
  27. ↑ Van de Kar LD, Li Q, Cabrera TM, Brownfield MS, Battaglia G (July 1998). "Alterations in 8-hydroxy-2-(dipropylamino)tetralin-induced neuroendocrine responses after 5,7-dihydroxytryptamine-induced denervation of serotonergic neurons". J Pharmacol Exp Ther. 286 (1): 256–262. PMID   9655867.
  28. ↑ Jørgensen H, Riis M, Knigge U, Kjaer A, Warberg J (March 2003). "Serotonin receptors involved in vasopressin and oxytocin secretion". J Neuroendocrinol. 15 (3): 242–249. doi:10.1046/j.1365-2826.2003.00978.x. PMID   12588512.
  29. ↑ Aubert Y, Allers KA, Sommer B, de Kloet ER, Abbott DH, Datson NA (June 2013). "Brain region-specific transcriptomic markers of serotonin-1A receptor agonist action mediating sexual rejection and aggression in female marmoset monkeys". J Sex Med. 10 (6): 1461–1475. doi:10.1111/jsm.12131. PMID   23551660.
  30. 1 2 Raap DK, Evans S, Garcia F, Li Q, Muma NA, Wolf WA, et al. (January 1999). "Daily injections of fluoxetine induce dose-dependent desensitization of hypothalamic 5-HT1A receptors: reductions in neuroendocrine responses to 8-OH-DPAT and in levels of Gz and Gi proteins". J Pharmacol Exp Ther. 288 (1): 98–106. PMID   9862759.
  31. ↑ Raap DK, Garcia F, Muma NA, Wolf WA, Battaglia G, van de Kar LD (February 1999). "Sustained desensitization of hypothalamic 5-Hydroxytryptamine1A receptors after discontinuation of fluoxetine: inhibited neuroendocrine responses to 8-hydroxy-2-(Dipropylamino)Tetralin in the absence of changes in Gi/o/z proteins". J Pharmacol Exp Ther. 288 (2): 561–567. PMID   9918559.
  32. ↑ Li Q, Wichems C, Heils A, Van De Kar LD, Lesch KP, Murphy DL (December 1999). "Reduction of 5-hydroxytryptamine (5-HT)(1A)-mediated temperature and neuroendocrine responses and 5-HT(1A) binding sites in 5-HT transporter knockout mice". J Pharmacol Exp Ther. 291 (3): 999–1007. PMID   10565817.
  33. ↑ Van de Kar LD, Raap DK, Battaglia G, Muma NA, Garcia F, DonCarlos LL (July 2002). "Treatment of cycling female rats with fluoxetine induces desensitization of hypothalamic 5-HT(1A) receptors with no change in 5-HT(2A) receptors". Neuropharmacology. 43 (1): 45–54. doi:10.1016/s0028-3908(02)00075-8. PMID   12213258.
  34. ↑ Raap DK, Van de Kar LD (1999). "Selective serotonin reuptake inhibitors and neuroendocrine function". Life Sci. 65 (12): 1217–1235. doi:10.1016/s0024-3205(99)00169-1. PMID   10503938. Gz proteins mediate the ACTH and oxytocin responses to 5-HT1A agonists (153,154). [...] 153. F. SERRES, D.K. RAAP, N.A. MUMA, F. GARCIA, G. BATTAGLIA, Y. ZHANG, Q. MA and L.D. VAN DE KAR, Soc. Neuroscience Abst. 24 539.18 (1998). (Abstract) 154. L.D. VAN DE KAR, Q. LI and G. BATTAGLIA, Soc. Neuroscience Abst. 24 539.17 (1998).(Abstract)
  35. ↑ Serres F, Li Q, Garcia F, Raap DK, Battaglia G, Muma NA, et al. (May 2000). "Evidence that G(z)-proteins couple to hypothalamic 5-HT(1A) receptors in vivo". J Neurosci. 20 (9): 3095–3103. doi:10.1523/JNEUROSCI.20-09-03095.2000. PMC   6773124 . PMID   10777773.
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