Serenic

A serenic, or antiaggressive agent, is a type of drug which reduces the capacity for irritability and aggression.[1]

Examples

The recreational drug MDMA ("ecstasy") and a variety of related drugs have been described as empathogen-entactogens, or simply as entactogens.[2] These agents possess serenic and empathy-increasing properties in addition to their euphoriant effects, and have been associated with increased sociability, friendliness, and feelings of closeness to others as well as emotional empathy and prosocial behavior.[3][4] The entactogenic effects of these drugs are thought to be related to their ability to temporarily increase the levels of certain brain chemicals, including serotonin,[5] dopamine, and, particularly, oxytocin.[3][6][7] Certain other serotonergic drugs, such as 5-HT1A receptor agonists, also increase oxytocin levels and may possess serenic properties as well.[8] The phenylpiperazine mixed 5-HT1A and 5-HT1B receptor agonists eltoprazine, fluprazine, and batoprazine have been described based on animal research as serenics.[9]

Agonists and antagonists of the receptors for the endogenous hormones oxytocin and vasopressin, respectively, have been shown to decrease aggressive behavior in scientific research, implicating them in the normal regulation of pathways involving aggressive behavior in the brain.[10][11] Certain neurosteroids, such as allopregnanolone, also appear to play a role in the regulation of aggression, including, notably, sexually-dimorphic aggressive behavior.[12] The sex hormones testosterone and estradiol also regulate aggression.

SRX-246 is a vasopressin 1A receptor antagonist that is under development by Azevan Pharmaceuticals for the treatment of intermittent explosive disorder (IED).[13] The results of a phase II clinical trial of the drug in the treatment of the condition are expected in the second quarter of 2016.[13][14]

As of 2007, there were no specific serenic drugs available to treat aggression in clinical use and commercially available.[15]

References

  1. ↑ Olivier, Berend; Mos, Jan (10 July 1986). Chan, Derwin K.C. (ed.). "Serenics and aggression". Stress & Health. Arlington, Virginia, United States of America: Wiley. 2 (3): 197–209. doi:10.1002/smi.2460020305. ISSN 1532-2998.
  2. ↑ Bedi, Gillinder; Hyman, David; de Wit, Harriet (December 2010). Krystal, John H. (ed.). "Is ecstasy an "empathogen"? Effects of ±3,4-methylenedioxymethamphetamine on prosocial feelings and identification of emotional states in others". Biological Psychiatry. Brentwood, Tennessee, United States of America: Society of Biological Psychiatry. 68 (12): 1134–1140. doi:10.1016/j.biopsych.2010.08.003. ISSN 0006-3223. LCCN 78009779. OCLC 424038458. PMC 2997873. PMID 20947066.
  3. 1 2 Hysek, Cédrik M.; Schmid, Yasmin; Simmler, Linda D.; Domes, Gregor; Heinrichs, Markus; Eisenegger, Christoph; Preller, Katrin H.; Quednow, Boris B.; Liechti, Matthias E. (28 October 2013). Lieberman, Matthew D. (ed.). "MDMA enhances emotional empathy and prosocial behavior". Social Cognitive and Affective Neuroscience. Oxford University Press. 9 (11): 1645–1652. doi:10.1093/scan/nst161. ISSN 1749-5016. PMC 4221206. PMID 24097374.
  4. ↑ Cami J, Farré M, Mas M, et al. (August 2000). "Human pharmacology of 3,4-methylenedioxymethamphetamine ("ecstasy"): psychomotor performance and subjective effects". J Clin Psychopharmacol. 20 (4): 455–66. doi:10.1097/00004714-200008000-00010. PMID 10917407.
  5. ↑ Piper, Brian J.; Fraiman, Joseph B.; Owens, Cullen B.; Ali, Syed F.; Meyer, Jerrold S. (1 April 2008). Carlezon, William A.; George, Tony P.; Neumaier, John F. (eds.). "Dissociation of the neurochemical and behavioral toxicology of MDMA ('Ecstasy') by citalopram". Neuropsychopharmacology. Brentwood, Tennessee, United States of America: American College of Neuropsychopharmacology (ACNP). 33 (5): 1192–1205. doi:10.1038/sj.npp.1301491. PMID 17609680.
  6. ↑ Dumont, C.J.H.; Sweep, F.C.G.; van der Steen, R.; Hermsen, R.; Donders, A.R.T.; Touw, D.J.; van Gerven, J.M.A.; van Gerven, M.A.; Buitelaar, J.K.; Verkes, R.J. (2009). Eslinger, Paul; Boggio, Paulo Sérgio; Young, Larry; Zahn, Roland (eds.). "Increased oxytocin concentrations and prosocial feelings in humans after ecstasy (3,4-methylenedioxymethamphetamine) administration". Social Neuroscience. London, United Kingdom of Great Britain: Society for Social Neuroscience/Taylor & Francis. 4 (4): 359–366. doi:10.1080/17470910802649470. ISSN 1747-0919. LCCN 2006244001. OCLC 69984013. PMID 19562632. S2CID 12310995.
  7. ↑ Broadbear, Jillian H.; Kabel, D.; Tracy, L.; Mak, P. (1 April 2014). Koob, George F.; Schulteis, Gery; Kantak, Kathleen M.; Arends, Michael A.; Buisman-Pijlman, Femke T.A.; Broadbear, Jillian H.; Sarnyai, Zoltán (eds.). "Oxytocinergic regulation of endogenous as well as drug-induced mood". Pharmacology Biochemistry and Behavior. Amsterdam, Netherlands: Elsevier. 119 (1): 61–71. doi:10.1016/j.pbb.2013.07.002. ISSN 0091-3057. LCCN 73644949. OCLC 1787728. PMID 23872370. S2CID 19772247. Retrieved 6 August 2021.
  8. ↑ de Boer, Sietse F.; Koolhaas, Jaap M. (1 December 2005). Redegeld, Frank A.; Verri, Waldiceu A.; Burk, Josh (eds.). "5-HT1A and 5-HT1B receptor agonists and aggression: A pharmacological challenge of the serotonin deficiency hypothesis". European Journal of Pharmacology. Amsterdam, Netherlands: Elsevier. 526 (1–3): 125–139. doi:10.1016/j.ejphar.2005.09.065. ISSN 0014-2999. LCCN sf97001017. OCLC 01568459. PMID 16310183. Retrieved 6 August 2021.
  9. ↑ Olivier, Berend (10 December 2004). "Serotonin and Aggression". Annals of the New York Academy of Sciences. New York City, New York, United States of America: New York Academy of Sciences. 1036 (1): 382–392. Bibcode:2004NYASA1036..382O. doi:10.1196/annals.1330.022. ISSN 0077-8923. LCCN 12037287. OCLC 01306678. PMID 15817750. S2CID 45595253. Retrieved 6 August 2021.
  10. ↑ Calcagnoli, Federica; de Boer, Sietse F.; Althaus, Monika; den Boer, Johan A.; Koolhaas, Jaap M. (October 2013). de Witt, Harriet; Curran, Valerie H.; Morrow, A. Leslie; Hashimoto, Kenji; Howes, Oliver; Floresco, Stan B.; D'Souza, Deepak (eds.). "Antiaggressive activity of central oxytocin in male rats". Psychopharmacology. Geneva, Switzerland: European Behavioural Pharmacology Society (EBPS)/Springer. 229 (4): 639–651. doi:10.1007/s00213-013-3124-7. PMID 23624810. S2CID 481042.
  11. ↑ Ferris, Craig F.; Lu, Shi-fang; Messenger, Tara; Guillon, Christophe D.; Heindel, Ned; Miller, Marvin; Koppel, Gary; Bruns, F. Robert; Simon, Neal G. (1 February 2006). Griebel, G.; Arends, M.A.; Izenwasser, S. (eds.). "Orally active vasopressin V1a receptor antagonist, SRX251, selectively blocks aggressive behavior". Pharmacology Biochemistry and Behavior. Amsterdam, Netherlands. 83 (2): 169–174. doi:10.1016/j.pbb.2006.01.001. ISSN 0091-3057. OCLC 67271683. PMID 16504276. S2CID 24199104.
  12. ↑ Pinna, Graziano; Agis-Balboa, Roberto Carlos; Pibiri, Fabio; Nelson, Marianela; Guidotti, Alessandro; Costa, Erminio (13 May 2008). Schousboe, Arne (ed.). "Neurosteroid biosynthesis regulates sexually dimorphic fear and aggressive behavior in mice". Neurochemical Research. Geneva, Switzerland: Springer. 33 (10): 1990–2007. doi:10.1007/s11064-008-9718-5. ISSN 0364-3190. PMID 18473173. S2CID 19338424. Retrieved 6 August 2021.
  13. 1 2 Fabio, Karine M.; Guillon, Christophe D.; Lu, Shi-Fang; Heindel, Ned D.; Brownstein, Michael J.; Lacey, Carl J.; Garippa, Carrie; Simon, Neal G. (2013). "Pharmacokinetics and Metabolism of SRX246: A Potent and Selective Vasopressin 1a Antagonist". Journal of Pharmaceutical Sciences. Amsterdam, Netherlands: Elsevier. 102 (6): 2033–2043. doi:10.1002/jps.23495. ISSN 0022-3549. PMID 23471831.
  14. ↑ Simon, Neal G. (5 May 2020). Rutter, Joni L. (ed.). "Developing SRX246 for Stress-Related Affective Illness". National Center for Advancing Translational Sciences (NCATS). Bethesda, Maryland, United States of America: National Institutes of Health. Retrieved 6 August 2021.
  15. ↑ Verhoeven, Willem M.A.; Tuinier, Sigfried (15 August 2007). Marazziti, Donatella; Schimmenti, Adriano (eds.). "Serenics: Anti-aggression drugs throughout history" (PDF). Clinical Neuropsychiatry: Journal of Treatments Evaluation. Rome, Italy: Giovanni Fioriti Editore. 4 (4): 135–143. ISSN 1724-4935. Retrieved 6 August 2021.


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