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-HT_1A receptor agonists, also increase oxytocin levels and may possess serenic properties as well.^[8] The phenylpiperazine mixed 5-HT_1A and 5-HT_1B 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.

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.^[13]^[14]^[15] 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.^[16]

References

^ 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.
^ 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.
^ ^a ^b 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.