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]

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

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. [11] [12] Certain neurosteroids, such as allopregnanolone, also appear to play a role in the regulation of aggression, including, notably, sexually-dimorphic aggressive behavior. [13] The sex hormones testosterone and estradiol also regulate aggression.

Antipsychotics, which are dopamine D2 receptor antagonists, are well-known as reducing aggression in humans and have been clinically employed for this purpose. [14] Molindone is under development for the treatment of impulsive aggression in children and adolescents with attention deficit hyperactivity disorder (ADHD). [15] [16]

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. [17] [18] [19] 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. [20]

Related Research Articles

<span class="mw-page-title-main">Empathogen</span> Class of psychoactive drugs that produce empathic experiences

Empathogens or entactogens are a class of psychoactive drugs that induce the production of experiences of emotional communion, oneness, relatedness, emotional openness—that is, empathy or sympathy—as particularly observed and reported for experiences with 3,4-methylenedioxymethamphetamine (MDMA). This class of drug is distinguished from the classes of hallucinogen or psychedelic, and amphetamine or stimulants. Major members of this class include MDMA, MDA, MDEA, MDOH, MBDB, 5-APB, 5-MAPB, 6-APB, 6-MAPB, methylone, mephedrone, GHB, αMT, and αET, MDAI among others. Most entactogens are phenethylamines and amphetamines, although several, such as αMT and αET, are tryptamines. When referring to MDMA and its counterparts, the term MDxx is often used. Entactogens are sometimes incorrectly referred to as hallucinogens or stimulants, although many entactogens such as ecstasy exhibit psychedelic or stimulant properties as well.

<span class="mw-page-title-main">5-HT receptor</span> Class of transmembrane proteins

5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in the central and peripheral nervous systems. They mediate both excitatory and inhibitory neurotransmission. The serotonin receptors are activated by the neurotransmitter serotonin, which acts as their natural ligand.

<span class="mw-page-title-main">Nicotinic acetylcholine receptor</span> Acetylcholine receptors named for their selective binding of nicotine

Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral nervous system, muscle, and many other tissues of many organisms. At the neuromuscular junction they are the primary receptor in muscle for motor nerve-muscle communication that controls muscle contraction. In the peripheral nervous system: (1) they transmit outgoing signals from the presynaptic to the postsynaptic cells within the sympathetic and parasympathetic nervous system, and (2) they are the receptors found on skeletal muscle that receive acetylcholine released to signal for muscular contraction. In the immune system, nAChRs regulate inflammatory processes and signal through distinct intracellular pathways. In insects, the cholinergic system is limited to the central nervous system.

<span class="mw-page-title-main">Serotonin receptor agonist</span> Neurotransmission-modulating substance

A serotonin receptor agonist is an agonist of one or more serotonin receptors. They activate serotonin receptors in a manner similar to that of serotonin, a neurotransmitter and hormone and the endogenous ligand of the serotonin receptors.

<span class="mw-page-title-main">Oxytocin receptor</span> Genes on human chromosome 3

The oxytocin receptor, also known as OXTR, is a protein which functions as receptor for the hormone and neurotransmitter oxytocin. In humans, the oxytocin receptor is encoded by the OXTR gene which has been localized to human chromosome 3p25.

A nicotinic agonist is a drug that mimics the action of acetylcholine (ACh) at nicotinic acetylcholine receptors (nAChRs). The nAChR is named for its affinity for nicotine.

5-HT<sub>1A</sub> receptor Serotonin receptor protein distributed in the cerebrum and raphe nucleus

The serotonin 1A receptor is a subtype of serotonin receptors, or 5-HT receptors, that binds serotonin, also known as 5-HT, a neurotransmitter. 5-HT1A is expressed in the brain, spleen, and neonatal kidney. It is a G protein-coupled receptor (GPCR), coupled to the Gi protein, and its activation in the brain mediates hyperpolarization and reduction of firing rate of the postsynaptic neuron. In humans, the serotonin 1A receptor is encoded by the HTR1A gene.

<span class="mw-page-title-main">8-OH-DPAT</span> Chemical compound

8-OH-DPAT is a research chemical of the aminotetralin chemical class which was developed in the 1980s and has been widely used to study the function of the 5-HT1A receptor. It was one of the first major 5-HT1A receptor full agonists to have been discovered.

<span class="mw-page-title-main">Alpha-7 nicotinic receptor</span> Type of cell receptor found in humans

The alpha-7 nicotinic receptor, also known as the α7 receptor, is a type of nicotinic acetylcholine receptor implicated in long-term memory, consisting entirely of α7 subunits. As with other nicotinic acetylcholine receptors, functional α7 receptors are pentameric [i.e., (α7)5 stoichiometry].

<span class="mw-page-title-main">Tebanicline</span> Chemical compound

Tebanicline is a potent synthetic nicotinic (non-opioid) analgesic drug developed by Abbott. It was developed as a less toxic analog of the potent poison dart frog-derived compound epibatidine, which is about 200 times stronger than morphine as an analgesic, but produces extremely dangerous toxic side effects. Like epibatidine, tebanicline showed potent analgesic activity against neuropathic pain in both animal and human trials, but with far less toxicity than its parent compound. It acts as a partial agonist at neuronal nicotinic acetylcholine receptors, binding to both the α3β4 and the α4β2 subtypes.

<span class="mw-page-title-main">Pozanicline</span> Synthetic nootropic drug

Pozanicline is a drug developed by Abbott, that has nootropic and neuroprotective effects. Animal studies suggested it useful for the treatment of ADHD and subsequent human trials have shown ABT-089 to be effective for this application. It binds with high affinity subtype-selective to the α4β2 nicotinic acetylcholine receptors and has partial agonism to the α6β2 subtype, but not the α7 and α3β4 subtypes familiar to nicotine. It has particularly low tendency to cause side effects compared to other drugs in the class.

<span class="mw-page-title-main">Monoamine releasing agent</span> Class of compounds

A monoamine releasing agent (MRA), or simply monoamine releaser, is a drug that induces the release of a monoamine neurotransmitter from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitter. Many drugs induce their effects in the body and/or brain via the release of monoamine neurotransmitters, e.g., trace amines, many substituted amphetamines, and related compounds.

<span class="mw-page-title-main">RU-24,969</span> Chemical compound

RU-24,969 is a serotonergic drug used in scientific research. It is a selective agonist of the serotonin 5-HT1A and 5-HT1B receptors, with 5-fold preference for the latter receptor over the former. It also has affinity for the serotonin 5-HT5A, 5-HT5B, and 5-HT7 receptors.

The alpha-3 beta-4 nicotinic receptor, also known as the α3β4 receptor and the ganglion-type nicotinic receptor, is a type of nicotinic acetylcholine receptor, consisting of α3 and β4 subunits. It is located in the autonomic ganglia and adrenal medulla, where activation yields post- and/or presynaptic excitation, mainly by increased Na+ and K+ permeability.

<span class="mw-page-title-main">Osemozotan</span> Pharmaceutical drug

Osemozotan (MKC-242) is a selective 5-HT1A receptor agonist with some functional selectivity, acting as a full agonist at presynaptic and a partial agonist at postsynaptic 5-HT1A receptors. 5-HT1A receptor stimulation influences the release of various neurotransmitters including serotonin, dopamine, norepinephrine, and acetylcholine. 5-HT1A receptors are inhibitory G protein-coupled receptor.

Hyperlocomotion, also known as locomotor hyperactivity, hyperactivity, or increased locomotor activity, is an effect of certain drugs in animals in which locomotor activity is increased. It is induced by certain drugs like psychostimulants and NMDA receptor antagonists and is reversed by certain other drugs like antipsychotics and certain antidepressants.

<span class="mw-page-title-main">GR-55562</span> 5-HT1B and 5-HT1D antagonist

GR-55562 is a selective serotonin 5-HT1B and 5-HT1D receptor antagonist. It is one of several selective serotonin 5-HT1B receptor antagonists used in scientific research.

<span class="mw-page-title-main">Tocinoic acid</span> Oxytocin receptor antagonist

Tocinoic acid is a peptide oxytocin receptor antagonist which is used in scientific research. Intracerebroventricular injection of the drug has been found to block the prosocial behavior induced by the serotonin releasing agent MDMA without affecting baseline social behavior in animals. Similar findings have been made for the non-peptide selective oxytocin receptor antagonist L-368899. However, in other studies, other oxytocin receptor antagonists have been ineffective in blocking MDMA-induced prosocial behavior. The reasons for these discrepancies are unclear.

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. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ "Molindone - Supernus Pharmaceuticals". AdisInsight. 29 May 2024. Retrieved 18 October 2024.
  16. ↑ 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.
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ 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.
  20. ↑ 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.
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