Serenic

Last updated
Serenic
Drug class
Class identifiers
Synonyms Anti-aggressive drug; Anti-aggressive agent; Anti-aggressive medication; Antiaggressive drug; Antiaggressive agent; Antiaggressive medication
UseTo reduce aggression and anger
Legal status
In Wikidata

A serenic, or anti-aggressive drug, is a type of drug which reduces the capacity for aggression. [1]

Contents

Examples

Serotonergic agents

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] The selective 5-HT1A biased full agonist F-15,599 (NLX-101) has shown antiaggressive effects in rodents as well. [10]

The serotonin 5-HT2C receptor agonist lorcaserin has been found to reduce impulsive aggression in people with intermittent explosive disorder (IED). [11] [12] [13] [14] Serotonin 5-HT2C receptor agonists have also been found to produce antiaggressive effects in rodents. [11]

The serotonergic psychedelics DOB and DOI, which act as serotonin 5-HT2 receptor agonists, show antiaggressive effects in rodents. [11] [15] [16] [17] However, DOI has also been found to have pro-aggressive effects. [11] In older literature, other psychedelics, including LSD, psilocin, dimethyltryptamine (DMT), and mescaline, have been found to reduce aggression in monkeys, but have also been found to increase aggression in animals in other contexts. [18] Serotonin 5-HT2A receptor antagonists have been found to reduce aggression in animals. [11] Atypical antipsychotics, which act in part as serotonin 5-HT2A receptor antagonists, have antiaggressive effects in humans. [11] The selective serotonin reuptake inhibitors (SSRIs) sertraline, fluvoxamine, and fluoxetine inhibited aggression in rodents, whereas the SSRIs citalopram and paroxetine were ineffective. [19] [20]

Antidopaminergic agents

Antipsychotics, which are dopamine D2 receptor antagonists, are well-known as reducing aggression in humans and have been clinically employed for this purpose. [21] Molindone is under development for the treatment of impulsive aggression in children and adolescents with attention deficit hyperactivity disorder (ADHD). [22] [23]

Beta blockers

Beta blockers, or β-adrenergic receptor antagonists, have been used to treat aggression and agitation. [24] Beta blockers that have been used for such purposes include propranolol, pindolol, and nadolol. [24]

Cholinergic agents

Nicotinic acetylcholine receptors within the CNS, specifically α7 homopentameric receptors, are implicated in the regulation of aggression. The serenic effect of nicotine is well documented both in laboratory animals and humans, and, conversely, nicotinic receptor antagonists and nicotine withdrawal are associated with irritability and aggression. [25] [26] [27] Additionally, nicotinic receptors are required for rabies virus entry into a neuron, and the dysfunction of these neurons is implicated in the rabies-associated aggression. [28]

Cannabinoids

Cannabinoids like nabilone have been studied and reported effective for management of severe aggression in people with profound autism and other intellectual and developmental disabilities. [29]

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. [30] [31] Certain neurosteroids, such as allopregnanolone, also appear to play a role in the regulation of aggression, including, notably, sexually-dimorphic aggressive behavior. [32] The sex hormones testosterone and estradiol regulate aggression as well. [33] [34] [35]

See also

References

  1. ↑ Olivier B, Mos J (10 July 1986). Chan DK (ed.). "Serenics and aggression" . Stress & Health. 2 (3). Arlington, Virginia, United States of America: Wiley: 197–209. doi:10.1002/smi.2460020305. ISSN   1532-2998.
  2. ↑ Bedi G, Hyman D, de Wit H (December 2010). Krystal JH (ed.). "Is ecstasy an "empathogen"? Effects of ±3,4-methylenedioxymethamphetamine on prosocial feelings and identification of emotional states in others". Biological Psychiatry. 68 (12). Brentwood, Tennessee, United States of America: Society of Biological Psychiatry: 1134–1140. doi:10.1016/j.biopsych.2010.08.003. LCCN   78009779. OCLC   424038458. PMC   2997873 . PMID   20947066.
  3. 1 2 Hysek CM, Schmid Y, Simmler LD, Domes G, Heinrichs M, Eisenegger C, et al. (November 2014). Lieberman MD (ed.). "MDMA enhances emotional empathy and prosocial behavior". Social Cognitive and Affective Neuroscience. 9 (11). Oxford University Press: 1645–1652. doi:10.1093/scan/nst161. PMC   4221206 . PMID   24097374.
  4. ↑ Cami J, Farré M, Mas M, Roset PN, Poudevida S, Mas A, et al. (August 2000). "Human pharmacology of 3,4-methylenedioxymethamphetamine ("ecstasy"): psychomotor performance and subjective effects". Journal of Clinical Psychopharmacology. 20 (4): 455–466. doi:10.1097/00004714-200008000-00010. PMID   10917407.
  5. ↑ Piper BJ, Fraiman JB, Owens CB, Ali SF, Meyer JS (April 2008). Carlezon WA, George TP, Neumaier JF (eds.). "Dissociation of the neurochemical and behavioral toxicology of MDMA ('Ecstasy') by citalopram". Neuropsychopharmacology. 33 (5). Brentwood, Tennessee, United States of America: American College of Neuropsychopharmacology (ACNP): 1192–1205. doi: 10.1038/sj.npp.1301491 . PMID   17609680.
  6. ↑ Dumont GJ, Sweep FC, van der Steen R, Hermsen R, Donders AR, Touw DJ, et al. (2009). Eslinger P, Boggio PS, Young L, Zahn R (eds.). "Increased oxytocin concentrations and prosocial feelings in humans after ecstasy (3,4-methylenedioxymethamphetamine) administration". Social Neuroscience. 4 (4). London, United Kingdom of Great Britain: Society for Social Neuroscience/Taylor & Francis: 359–366. doi:10.1080/17470910802649470. LCCN   2006244001. OCLC   69984013. PMID   19562632. S2CID   12310995.
  7. ↑ Broadbear JH, Kabel D, Tracy L, Mak P (April 2014). Koob JF, Schulteis G, Kantak KM, Arends M, Buisman-Pijlman FT, Broadbear JH, Zoltán S (eds.). "Oxytocinergic regulation of endogenous as well as drug-induced mood". Pharmacology, Biochemistry, and Behavior. 119 (1). Amsterdam, Netherlands: Elsevier: 61–71. doi:10.1016/j.pbb.2013.07.002. LCCN   73644949. OCLC   1787728. PMID   23872370. S2CID   19772247.
  8. ↑ de Boer SF, Koolhaas JM (December 2005). Redegeld FA, Verri WA, Burk J (eds.). "5-HT1A and 5-HT1B receptor agonists and aggression: a pharmacological challenge of the serotonin deficiency hypothesis". European Journal of Pharmacology. 526 (1–3). Amsterdam, Netherlands: Elsevier: 125–139. doi:10.1016/j.ejphar.2005.09.065. LCCN   sf97001017. OCLC   01568459. PMID   16310183.
  9. ↑ Olivier B (December 2004). "Serotonin and aggression". Annals of the New York Academy of Sciences. 1036 (1). New York City, New York, United States of America: New York Academy of Sciences: 382–392. Bibcode:2004NYASA1036..382O. doi:10.1196/annals.1330.022. LCCN   12037287. OCLC   01306678. PMID   15817750. S2CID   45595253.
  10. ↑ Sałaciak K, Pytka K (November 2021). "Biased agonism in drug discovery: Is there a future for biased 5-HT1A receptor agonists in the treatment of neuropsychiatric diseases?". Pharmacol Ther. 227: 107872. doi: 10.1016/j.pharmthera.2021.107872 . PMID   33905796.
  11. 1 2 3 4 5 6 Popova NK, Tsybko AS, Naumenko VS (August 2022). "The Implication of 5-HT Receptor Family Members in Aggression, Depression and Suicide: Similarity and Difference". Int J Mol Sci. 23 (15): 8814. doi: 10.3390/ijms23158814 . PMC   9369404 . PMID   35955946. There are some pharmacological data indicating a link between aggressive behavior and 5-HT2A receptor activity. In animals, 5-HT2A agonists, such as DOI, reduced aggressive behavior in flies, amphibians, mice and rats [34]. However, accumulated data also revealed a pro-aggressive effect of the 5-HT2A agonist DOI [119,120], whereas 5-HT2A antagonists effectively suppressed aggressive behavior [119,121,122]. In humans, a number of atypical antipsychotics, which act as antagonists of 5-HT2A receptors, had antiaggressive effects in clinical trials reviewed by Comai and co-authors [123]. [...] There are a few currently available data in support of the antiaggressive role of 5-HT2C receptors: (1) the activation of 5-HT2C receptors enhanced the display of defeat submissive and defensive behavior in golden hamsters [172]. (2) 5-HT2C receptor agonist/alpha 2 receptor antagonist S32212 suppressed aggressive behavior in mice [173]. (3) Mice expressing only the VGV isoform of 5-HT2C receptors displayed a high level of conspecific aggression [174]. (4) The association between Htr2c gene polymorphism and criminal behavior in humans was demonstrated [175]. (5) Recently, a novel 5-HT2C agonist, lorcaserin, has been demonstrated to have antiaggressive properties in human subjects with impulsive aggressive behavior. Lorcaserin attenuated provoked, but not unprovoked, aggression in impulsively aggressive individuals indicating that 5-HT2C receptor may be a putative target for the treatment of impulsive aggressive behavior in human subjects [176].
  12. ↑ Desilva, Nilifa; Hollander, Eric (2023). "Impulse Control Disorders: Intermittent Explosive Disorder, Kleptomania, Pyromania". Tasman's Psychiatry. Cham: Springer International Publishing. p. 1–49. doi:10.1007/978-3-030-42825-9_165-1. ISBN   978-3-030-42825-9. Based on evidence from a recent pilot study, lorcaserin, a selective 5-HT2c agonist, was found to have anti-aggressive effects in humans with high levels of impulsive aggression like in those diagnosed with IED.
  13. ↑ Tahir T, Wong MM, Maaz M, Naufal R, Tahir R, Naidoo Y (May 2022). "Pharmacotherapy of impulse control disorders: A systematic review". Psychiatry Res. 311: 114499. doi:10.1016/j.psychres.2022.114499. PMID   35305343.
  14. ↑ Coccaro EF, Lee RJ (November 2019). "5-HT2c agonist, lorcaserin, reduces aggressive responding in intermittent explosive disorder: A pilot study". Hum Psychopharmacol. 34 (6): e2714. doi:10.1002/hup.2714. PMID   31774584.
  15. ↑ Morrison TR, Melloni RH (2014). "The role of serotonin, vasopressin, and serotonin/vasopressin interactions in aggressive behavior". Curr Top Behav Neurosci. 17: 189–228. doi:10.1007/7854_2014_283. PMID   24496652. Another 5HT2A receptor partial agonist, DOB, has a marginally higher affinity for the 5HT2A receptor (in its low affinity state) than DOI (Roth et al. 1997), and in the water competition (WC) test it has been shown to block defensive aggression in rats. Interestingly, DOI also reduced the number of offensive aggressive behaviors (i.e., attacks, greater latency to first attack, shorter attack duration) in the same animals that exhibited DOI-induced reductions in defensive behaviors during the WC test (Muehlenkamp et al. 1995).
  16. ↑ Muehlenkamp F, Lucion A, Vogel WH (April 1995). "Effects of selective serotonergic agonists on aggressive behavior in rats". Pharmacology Biochemistry and Behavior. 50 (4): 671–674. doi:10.1016/0091-3057(95)00351-7. PMID   7617717. S2CID   12774131.
  17. ↑ Sakaue M, Ago Y, Sowa C, Sakamoto Y, Nishihara B, Koyama Y, Baba A, Matsuda T (May 2002). "Modulation by 5-hT2A receptors of aggressive behavior in isolated mice". Jpn J Pharmacol. 89 (1): 89–92. doi: 10.1254/jjp.89.89 . PMID   12083749.
  18. ↑ Martin, W. R.; Sloan, J. W. (1977). "Pharmacology and Classification of LSD-like Hallucinogens". Drug Addiction II: Amphetamine, Psychotogen, and Marihuana Dependence. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 305–368. doi:10.1007/978-3-642-66709-1_3. ISBN   978-3-642-66711-4.
  19. ↑ Miczek KA, Fish EW, De Bold JF, De Almeida RM (October 2002). "Social and neural determinants of aggressive behavior: pharmacotherapeutic targets at serotonin, dopamine and gamma-aminobutyric acid systems". Psychopharmacology (Berl). 163 (3–4): 434–458. doi:10.1007/s00213-002-1139-6. PMID   12373445.
  20. ↑ Sánchez C, Meier E (February 1997). "Behavioral profiles of SSRIs in animal models of depression, anxiety and aggression. Are they all alike?". Psychopharmacology (Berl). 129 (3): 197–205. doi:10.1007/s002130050181. PMID   9084057.
  21. ↑ Itil TM, Wadud A (February 1975). "Treatment of human aggression with major tranquilizers, antidepressants, and newer psychotropic drugs". J Nerv Ment Dis. 160 (2–1): 83–99. doi:10.1097/00005053-197502000-00003. PMID   235010.
  22. ↑ "Molindone - Supernus Pharmaceuticals". AdisInsight. 29 May 2024. Retrieved 18 October 2024.
  23. ↑ Robb AS, Schwabe S, Ceresoli-Borroni G, Nasser A, Yu C, Marcus R, Candler SA, Findling RL (March 2019). "A proposed anti-maladaptive aggression agent classification: improving our approach to treating impulsive aggression". Postgrad Med. 131 (2): 129–137. doi: 10.1080/00325481.2019.1574401 . PMID   30678534.
  24. 1 2 Boyce TG, Ballone NT, Certa KM, Becker MA (2021). "The Use of β-Adrenergic Receptor Antagonists in Psychiatry: A Review". J Acad Consult Liaison Psychiatry. 62 (4): 404–412. doi:10.1016/j.jaclp.2020.12.009. PMID   34210401.
  25. ↑ Lewis AS, Picciotto MR (May 2020). "Regulation of aggressive behaviors by nicotinic acetylcholine receptors: Animal models, human genetics, and clinical studies". Neuropharmacology. 167: 107929. doi:10.1016/j.neuropharm.2019.107929. PMC   7080580 . PMID   32058178.
  26. ↑ Lewis AS, Mineur YS, Smith PH, Cahuzac EL, Picciotto MR (October 2015). "Modulation of aggressive behavior in mice by nicotinic receptor subtypes". Biochemical Pharmacology. Nicotinic Acetylcholine Receptors as Therapeutic Targets: Emerging Frontiers in Basic Research and Clinical Science (Satellite to the 2015 Meeting of the Society for Neuroscience) Oct 14-15, Chicago, IL USA. 97 (4): 488–497. doi:10.1016/j.bcp.2015.07.019. PMC   4600457 . PMID   26212554.
  27. ↑ Picciotto MR, Lewis AS, van Schalkwyk GI, Mineur YS (September 2015). "Mood and anxiety regulation by nicotinic acetylcholine receptors: A potential pathway to modulate aggression and related behavioral states". Neuropharmacology. The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition. 96 (Pt B): 235–243. doi:10.1016/j.neuropharm.2014.12.028. PMC   4486625 . PMID   25582289.
  28. ↑ Hueffer K, Khatri S, Rideout S, Harris MB, Papke RL, Stokes C, Schulte MK (October 2017). "Rabies virus modifies host behaviour through a snake-toxin like region of its glycoprotein that inhibits neurotransmitter receptors in the CNS". Scientific Reports. 7 (1): 12818. Bibcode:2017NatSR...712818H. doi:10.1038/s41598-017-12726-4. PMC   5634495 . PMID   28993633.
  29. ↑ Lin, Hsiang-Yuan; Abi-Jaoude, Elia; Desarkar, Pushpal; Wang, Wei; Ameis, Stephanie H.; Lai, Meng-Chuan; Lunsky, Yona; Rajji, Tarek (2025). "364. Nabilone for Severe Aggression in Adults With Profound Autism or Intellectual and Developmental Disabilities: A Phase I Open-Label Clinical Trial" . Biological Psychiatry. 97 (9): S246. doi:10.1016/j.biopsych.2025.02.602 . Retrieved 6 May 2025.
  30. ↑ Calcagnoli F, de Boer SF, Althaus M, den Boer JA, Koolhaas JM (October 2013). de Witt H, Curran VH, Morrow AL, Hashimoto K, Howes O, Floresco SB, D'Souza D (eds.). "Antiaggressive activity of central oxytocin in male rats". Psychopharmacology. 229 (4). Geneva, Switzerland: European Behavioural Pharmacology Society (EBPS)/Springer: 639–651. doi:10.1007/s00213-013-3124-7. PMID   23624810. S2CID   481042.
  31. ↑ Ferris CF, Lu SF, Messenger T, Guillon CD, Heindel N, Miller M, et al. (February 2006). Griebel G, Arends MA, Izenwasser S (eds.). "Orally active vasopressin V1a receptor antagonist, SRX251, selectively blocks aggressive behavior". Pharmacology, Biochemistry, and Behavior. 83 (2). Amsterdam, Netherlands: 169–174. doi:10.1016/j.pbb.2006.01.001. OCLC   67271683. PMID   16504276. S2CID   24199104.
  32. ↑ Pinna G, Agis-Balboa RC, Pibiri F, Nelson M, Guidotti A, Costa E (October 2008). Schousboe A (ed.). "Neurosteroid biosynthesis regulates sexually dimorphic fear and aggressive behavior in mice". Neurochemical Research. 33 (10). Geneva, Switzerland: Springer: 1990–2007. doi:10.1007/s11064-008-9718-5. PMID   18473173. S2CID   19338424.
  33. ↑ Cunningham RL, Lumia AR, McGinnis MY (2012). "Androgen receptors, sex behavior, and aggression". Neuroendocrinology. 96 (2): 131–140. doi:10.1159/000337663. PMC   3474193 . PMID   22414851.
  34. ↑ Giammanco M, Tabacchi G, Giammanco S, Di Majo D, La Guardia M (April 2005). "Testosterone and aggressiveness". Med Sci Monit. 11 (4): RA136–45. PMID   15795710.
  35. ↑ Albert DJ, Jonik RH, Walsh ML (1992). "Hormone-dependent aggression in male and female rats: experiential, hormonal, and neural foundations". Neurosci Biobehav Rev. 16 (2): 177–192. doi:10.1016/s0149-7634(05)80179-4. PMID   1630729.
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