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Serenic

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

The recreational drug MDMA ("ecstasy") and a variety of related drugs have been described as empathogen-entactogens, or simply as entactogens. 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. 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, dopamine, and, particularly, oxytocin.

Certain other serotonergic drugs, such as 5-HT1A receptor agonists, also increase oxytocin levels and may possess serenic properties as well. The phenylpiperazine mixed 5-HT1A and 5-HT1B receptor agonists eltoprazine, fluprazine, and batoprazine have been described based on animal research as serenics. The selective 5-HT1A biased full agonist F-15,599 (NLX-101) has shown antiaggressive effects in rodents as well.

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

The serotonergic psychedelics DOB and DOI, which act as serotonin 5-HT2 receptor agonists, show antiaggressive effects in rodents. However, DOI has also been found to have pro-aggressive effects. 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. Serotonin 5-HT2A receptor antagonists have been found to reduce aggression in animals. Atypical antipsychotics, which act in part as serotonin 5-HT2A receptor antagonists, have antiaggressive effects in humans. The selective serotonin reuptake inhibitors (SSRIs) sertraline, fluvoxamine, and fluoxetine inhibited aggression in rodents, whereas the SSRIs citalopram and paroxetine were ineffective.

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

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

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. 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.

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