s such as tryptamines, lysergamides ), phenethylamines, and amphetamines are non-selective agonists of serotonin receptors. Their hallucinogenic effects are specifically mediated by activation of the 5-HT2A receptor. Drugs that increase extracellular serotonin levels such as serotonin reuptake inhibitors, serotonin releasing agents, and monoamine oxidase inhibitors are indirect non-selective serotonin receptor agonists. They are used variously as antidepressants, anxiolytics, antiobsessionals, appetite suppressants, and entactogens.
In addition to being 5-HT1B agonists, triptans are also agonists at the 5-HT1D receptor, which contributes to their antimigraine effect caused by vasoconstriction of blood vessels in the brain. The same is true for ergotamine.
Triptans such as eletriptan, naratriptan, and sumatriptan are agonists of the 5-HT1F receptor. Lasmiditan is a selective 5-HT1F agonist that is under development by Eli Lilly and Company for the treatment of migraine.
5-HT2 receptor agonists
5-HT2A receptor agonists
Serotonergic psychedelics like psilocybin, LSD, and mescaline act as 5-HT2A receptor agonists. Their actions at this receptor are thought to be responsible for their hallucinogenic effects. Most of these drugs also act as agonists of other serotonin receptors. Not all 5-HT2A receptor agonists are psychoactive. The 25-NB series is a family of phenethylamine serotonergic psychedelics that, unlike other classes of serotonergic psychedelics, act as highly selective 5-HT2A receptor agonists. The most well-known member of the 25-NB series is 25I-NBOMe. -DMBMPP is an analogue of the 25-NB compounds and is the most highly selective agonist of the 5-HT2A receptor that has been identified to date. O-4310 is a tryptamine derivative that is a highly selective agonist of the 5-HT2A receptor. Selective 5-HT2A receptor agonists like the 25-NB compounds can cause serotonin syndrome-like adverse effects such as hyperthermia, hyperpyrexia, tachycardia, hypertension, clonus, seizures, agitation, aggression, and hallucinations, most importantly in overdose. In severe cases, these effects can be fatal. In contrast, for reasons that are unknown, LSD, which is an agonist of both the 5-HT2A receptor and many other serotonin receptors, has never been associated with serotonin syndrome in more than 50 years of use. Activation of the 5-HT2A receptor is also implicated in serotonin syndrome caused by indirect serotonin receptor agonists like serotonin reuptake inhibitors, serotonin releasing agents, and monoamine oxidase inhibitors. Antagonists of the 5-HT2A receptor like cyproheptadine and chlorpromazine are able to reverse and mediate recovery from serotonin syndrome.
5-HT2B receptor agonists
Agonists of the 5-HT2B receptor are implicated in the development of cardiac fibrosis. Fenfluramine, pergolide, and cabergoline have been withdrawn from some markets for this reason. Many serotonergic psychedelics, such as LSD and psilocin, have been shown to activate this receptor directly. MDMA has been reported to be both a potent direct agonist and have an indirect effect by increasing plasma serotonin levels.
5-HT2C receptor agonists
is an appetite suppressant and anti-obesity drug which acts as a selective 5-HT2C receptor agonist. meta-Chlorophenylpiperazine is a 5-HT2C-preferring serotonin receptor agonist that induces anxiety and depression and can cause panic attacks in susceptible individuals.
5-HT3 receptor agonists
and quipazine are moderately selective agonists of the 5-HT3 receptor that are used in scientific research. Agonists of this receptor are known to induce nausea and vomiting, and are not used medically.
5-HT4 receptor agonists
and tegaserod are 5-HT4 receptor partial agonists that were used to treat disorders of gastrointestinal motility. Prucalopride is a highly selective 5-HT4 receptor agonist that can be used to treat certain disorders of gastrointestinal motility. Other 5-HT4 receptor agonists have shown potential to be nootropic and antidepressant drugs, but have not been marketed for such indications.
5-HT5A receptor agonists
, a constituent of valerian root, has been found to act as a 5-HT5A receptor agonist, and this action could be involved in the sleep-promoting effects of valerian.
