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]

As of yet, there are no specific serenic drugs available to treat aggression or other conditions in clinical use.[14][15] However, various atypical antipsychotics have been found effective and are approved and used specifically in the treatment of aggression/irritability in autism and Alzheimer's disease.

References

  1. ↑ Olivier, Berend; Mos, Jan (1986). "Serenics and aggression". Stress Medicine. 2 (3): 197–209. doi:10.1002/smi.2460020305. ISSN 0748-8386.
  2. ↑ Bedi G, Hyman D, de Wit H (December 2010). "Is ecstasy an "empathogen"? Effects of ±3,4-methylenedioxymethamphetamine on prosocial feelings and identification of emotional states in others". Biol. Psychiatry. 68 (12): 1134–40. doi:10.1016/j.biopsych.2010.08.003. PMC 2997873Freely accessible. PMID 20947066.
  3. 1 2 Hysek CM, Schmid Y, Simmler LD, et al. (October 2013). "MDMA enhances emotional empathy and prosocial behavior". Soc Cogn Affect Neurosci. 9: 1645–52. doi:10.1093/scan/nst161. 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 BJ, Fraiman JB, Owens CB, Ali SF, Meyer JS (April 2008). "Dissociation of the neurochemical and behavioral toxicology of MDMA ('Ecstasy') by citalopram". Neuropsychopharmacology. 33 (5): 1192–205. doi:10.1038/sj.npp.1301491. PMID 17609680.
  6. ↑ Dumont GJ, Sweep FC, van der Steen R, et al. (2009). "Increased oxytocin concentrations and prosocial feelings in humans after ecstasy (3,4-methylenedioxymethamphetamine) administration". Soc Neurosci. 4 (4): 359–66. doi:10.1080/17470910802649470. PMID 19562632.
  7. ↑ Broadbear JH, Kabel D, Tracy L, Mak P (April 2014). "Oxytocinergic regulation of endogenous as well as drug-induced mood". Pharmacol. Biochem. Behav. 119: 61–71. doi:10.1016/j.pbb.2013.07.002. PMID 23872370.
  8. ↑ de Boer SF, Koolhaas JM (December 2005). "5-HT1A and 5-HT1B receptor agonists and aggression: a pharmacological challenge of the serotonin deficiency hypothesis". Eur. J. Pharmacol. 526 (1-3): 125–39. doi:10.1016/j.ejphar.2005.09.065. PMID 16310183.
  9. ↑ Olivier, Berend (2006). "Serotonin and Aggression". Annals of the New York Academy of Sciences. 1036 (1): 382–392. doi:10.1196/annals.1330.022. ISSN 0077-8923.
  10. ↑ Calcagnoli F, de Boer SF, Althaus M, den Boer JA, Koolhaas JM (October 2013). "Antiaggressive activity of central oxytocin in male rats". Psychopharmacology (Berl.). 229 (4): 639–51. doi:10.1007/s00213-013-3124-7. PMID 23624810.
  11. ↑ Ferris CF, Lu SF, Messenger T, et al. (February 2006). "Orally active vasopressin V1a receptor antagonist, SRX251, selectively blocks aggressive behavior". Pharmacol. Biochem. Behav. 83 (2): 169–74. doi:10.1016/j.pbb.2006.01.001. PMID 16504276.
  12. ↑ Pinna G, Agis-Balboa RC, Pibiri F, Nelson M, Guidotti A, Costa E (October 2008). "Neurosteroid biosynthesis regulates sexually dimorphic fear and aggressive behavior in mice". Neurochem. Res. 33 (10): 1990–2007. doi:10.1007/s11064-008-9718-5. PMID 18473173.
  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. 102 (6): 2033–2043. doi:10.1002/jps.23495. ISSN 0022-3549.
  14. ↑ Verhoeven, W.M.A., & Tuinier, S.. (2007). Serenics: Anti-aggression drugs throughout history. Clinical Neuropsychiatry: journal of treatments evaluation, 135–143. Retrieved from http://hdl.handle.net/1765/14916
  15. ↑ PDF Document: http://www.clinicalneuropsychiatry.org/pdf/01_verhoeven.pdf Source: http://www.clinicalneuropsychiatry.org/risultatiRicerca.php#


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