Chemistry:8-OH-DPAT

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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.

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. ↑ "Concepts for the design of 5-HT 1A serotonin agonists and antagonists". Drug Development Research 26 (3): 251–274. 1992. doi:10.1002/ddr.430260306. ISSN 0272-4391. https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/ddr.430260306. Retrieved 19 November 2025. 
  2. ↑ The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds. 1. Berkeley: Transform Press. 2011. ISBN 978-0-9630096-3-0. 
  3. ↑ "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. February 1990. doi:10.1016/0028-3908(90)90047-U. PMID 1691832. 
  4. ↑ "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. January 2004. doi:10.1016/j.neuropharm.2003.08.007. PMID 14654097. 
  5. ↑ "IUPHAR DATABASE - 5-Hydroxytryptamine receptors - 5-HT7". http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2337. 
  6. ↑ "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. November 1996. doi:10.1111/j.1476-5381.1996.tb15749.x. PMID 8922730. 
  7. ↑ "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. February 1992. doi:10.1007/BF00165727. PMID 1570019. 
  8. ↑ "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. March 1993. doi:10.1111/j.1476-5381.1993.tb12859.x. PMID 8467355. 
  9. ↑ "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. November 1993. doi:10.1016/0014-2999(93)90531-L. PMID 7904566. 
  10. ↑ 10.0 10.1 "A role for oxytocin and 5-HT(1A) receptors in the prosocial effects of 3,4 methylenedioxymethamphetamine ("ecstasy")". Neuroscience 146 (2): 509–514. May 2007. doi:10.1016/j.neuroscience.2007.02.032. PMID 17383105. 
  11. ↑ 11.0 11.1 11.2 11.3 "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. July 2020. doi:10.1177/0269881120913150. PMID 32312154. 
  12. ↑ "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. December 2005. doi:10.1016/j.ejphar.2005.09.065. PMID 16310183. 
  13. ↑ 13.0 13.1 "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. January 2015. doi:10.1111/jsm.12742. PMID 25359190. 
  14. ↑ "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. October 1985. doi:10.1016/0361-9230(85)90005-X. PMID 2933126. 
  15. ↑ "Antiemetic effects of flesinoxan in cats: comparisons with 8-hydroxy-2-(di-n-propylamino)tetralin". European Journal of Pharmacology 253 (1–2): 53–60. February 1994. doi:10.1016/0014-2999(94)90756-0. PMID 8013549. 
  16. ↑ "Evidence for postsynaptic mediation of the hypothermic effect of 5-HT1A receptor activation". British Journal of Pharmacology 106 (3): 603–609. July 1992. doi:10.1111/j.1476-5381.1992.tb14382.x. PMID 1387027. 
  17. ↑ 17.0 17.1 "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. March 1987. doi:10.1097/00005344-198703000-00010. PMID 2437400. 
  18. ↑ "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. February 2000. doi:10.1016/S0022-3565(24)35342-X. PMID 10640309. 
  19. ↑ "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. February 2006. doi:10.1152/ajpregu.00440.2005. PMID 16166206. 
  20. ↑ "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. April 2009. doi:10.1213/ane.0b013e318198f828. PMID 19299781. 
  21. ↑ "Serotonin receptor subtypes in spinal antinociception in the rat". The Journal of Pharmacology and Experimental Therapeutics 269 (3): 1182–1189. June 1994. doi:10.1016/S0022-3565(25)38857-9. PMID 8014862. http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8014862. 
  22. ↑ "Stimulation of 5-HT1A and 5-HT2/5-HT1C receptors induce oxytocin release in the male rat". Brain Res 611 (2): 330–332. May 1993. doi:10.1016/0006-8993(93)90521-n. PMID 8334526. 
  23. ↑ "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. December 1993. doi:10.1016/0006-8993(93)90652-4. PMID 8118681. 
  24. ↑ "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. 1996. doi:10.1016/s0028-3908(96)00078-0. PMID 9025112. 
  25. ↑ "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. November 1996. PMID 8930214. 
  26. ↑ "WAY-100635 inhibits 8-OH-DPAT-stimulated oxytocin, ACTH and corticosterone, but not prolactin secretion". Eur J Pharmacol 346 (2-3): 261–266. April 1998. doi:10.1016/s0014-2999(97)01607-5. PMID 9652368. 
  27. ↑ "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. July 1998. PMID 9655867. 
  28. ↑ "Serotonin receptors involved in vasopressin and oxytocin secretion". J Neuroendocrinol 15 (3): 242–249. March 2003. doi:10.1046/j.1365-2826.2003.00978.x. PMID 12588512. 
  29. ↑ "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. June 2013. doi:10.1111/jsm.12131. PMID 23551660. 
  30. ↑ 30.0 30.1 "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. January 1999. PMID 9862759. 
  31. ↑ "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. February 1999. PMID 9918559. 
  32. ↑ "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. December 1999. PMID 10565817. 
  33. ↑ "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. July 2002. doi:10.1016/s0028-3908(02)00075-8. PMID 12213258. 
  34. ↑ "Selective serotonin reuptake inhibitors and neuroendocrine function". Life Sci 65 (12): 1217–1235. 1999. 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. ↑ "Evidence that G(z)-proteins couple to hypothalamic 5-HT(1A) receptors in vivo". J Neurosci 20 (9): 3095–3103. May 2000. doi:10.1523/JNEUROSCI.20-09-03095.2000. PMID 10777773. 



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