“Serotonin receptor agonist”的意思、由来-开放百科全书

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 (5-hydroxytryptamine; 5-HT), a neurotransmitter and hormone and the endogenous ligand of the serotonin receptors.

Non-selective agonists

Serotonergic psychedelics such as tryptamines (e.g., psilocybin, psilocin, {{abbrlink|DMT|dimethyltryptamine}}, 5-MeO-DMT, bufotenin), lysergamides (e.g., {{abbrlink|LSD|lysergic acid diethylamide}}, ergine ({{abbr|LSA|lysergic acid amide}})), phenethylamines (e.g., mescaline, 2C-B, 25I-NBOMe), and amphetamines (e.g., {{abbrlink|MDA|3,4-methylenedioxyamphetamine}}, {{abbrlink|DOM|2,5-dimethoxy-4-methylamphetamine}}) are non-selective agonists of serotonin receptors. Their hallucinogenic effects are specifically mediated by activation of the 5-HT_2A receptor.

Drugs that increase extracellular serotonin levels such as serotonin reuptake inhibitors (e.g., fluoxetine, venlafaxine), serotonin releasing agents (e.g., fenfluramine, {{abbrlink|MDMA|methylenedioxymethamphetamine}}), and monoamine oxidase inhibitors (e.g., phenelzine, moclobemide) are indirect non-selective serotonin receptor agonists. They are used variously as antidepressants, anxiolytics, antiobsessionals, appetite suppressants, and entactogens.

5-HT₁ receptor agonists

5-HT_1A receptor agonists

Azapirones such as buspirone, gepirone, and tandospirone are 5-HT_1A receptor partial agonists marketed primarily as anxiolytics, but also as antidepressants. The antidepressants vilazodone and vortioxetine are 5-HT_1A receptor partial agonists. Flibanserin, a drug used for female sexual dysfunction, is a 5-HT_1A receptor partial agonist. Many atypical antipsychotics, such as aripiprazole, asenapine, clozapine, lurasidone, quetiapine, and ziprasidone, are 5-HT_1A receptor partial agonists, and this action is thought to contribute to their beneficial effects on negative symptoms in schizophrenia.

5-HT_1B receptor agonists

Triptans such as sumatriptan, rizatriptan, and naratriptan are 5-HT_1B receptor agonists that are used to abort migraine and cluster headache attacks. The ergoline antimigraine agent ergotamine also acts on this receptor.

5-HT_1D receptor agonists

In addition to being 5-HT_1B agonists, triptans (i.e. sumatriptan, almotriptan, zolmitriptan, naratriptan, eletriptan, frovatriptan and rizatriptan) are also agonists at the 5-HT_1D receptor, which contributes to their antimigraine effect caused by vasoconstriction of blood vessels in the brain. The same is true for ergotamine.

5-HT_1E receptor agonists

The triptan eletriptan is an agonist of the 5-HT_1E receptor. BRL-54443 is a selective 5-HT_1E and 5-HT_1F receptor agonist which is used in scientific research.

5-HT_1F receptor agonists

Triptans such as eletriptan, naratriptan, and sumatriptan are agonists of the 5-HT_1F receptor. Lasmiditan is a selective 5-HT_1F agonist that is under development by Eli Lilly and Company for the treatment of migraine.^[2]^[3]

5-HT₂ receptor agonists

5-HT_2A receptor agonists

Serotonergic psychedelics like psilocybin, LSD, and mescaline act as 5-HT_2A 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-HT_2A receptor agonists are psychoactive.^[4]

The 25-NB (NBOMe) series is a family of phenethylamine serotonergic psychedelics that, unlike other classes of serotonergic psychedelics, act as highly selective 5-HT_2A receptor agonists.^[5] The most well-known member of the 25-NB series is 25I-NBOMe.^[6]^[7] (2S,6S)-DMBMPP is an analogue of the 25-NB compounds and is the most highly selective agonist of the 5-HT_2A receptor that has been identified to date.^[8] O-4310 (1-isopropyl-6-fluoropsilocin) is a tryptamine derivative that is a highly selective agonist of the 5-HT_2A receptor.^[9]

Selective 5-HT_2A 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.^[7]^[10]^[11] In severe cases, these effects can be fatal.^[7]^[10] In contrast, for reasons that are unknown, LSD, which is an agonist of both the 5-HT_2A receptor and many other serotonin receptors, has never been associated with serotonin syndrome in more than 50 years of use.^[10] Activation of the 5-HT_2A receptor is also implicated in serotonin syndrome caused by indirect serotonin receptor agonists like serotonin reuptake inhibitors, serotonin releasing agents, and monoamine oxidase inhibitors.^[10]^[12] Antagonists of the 5-HT_2A receptor like cyproheptadine and chlorpromazine are able to reverse and mediate recovery from serotonin syndrome.^[13]

5-HT_2B receptor agonists

Agonists of the 5-HT_2B receptor are implicated in the development of cardiac fibrosis.^[14] Fenfluramine, pergolide, and cabergoline have been withdrawn from some markets for this reason.^[15] Many serotonergic psychedelics, such as LSD and psilocin, have been shown to activate this receptor directly.^[16] MDMA has been reported to be both a potent direct agonist^[14] and have an indirect effect by increasing plasma serotonin levels.^[17]

5-HT_2C receptor agonists

Lorcaserin is an appetite suppressant and anti-obesity drug which acts as a selective 5-HT_2C receptor agonist. meta-Chlorophenylpiperazine (mCPP) is a 5-HT_2C-preferring serotonin receptor agonist that induces anxiety and depression and can cause panic attacks in susceptible individuals.

5-HT₃ receptor agonists

2-Methyl-5-hydroxytryptamine (2-methylserotonin) 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

Cisapride 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-HT_5A receptor agonists

Valerenic acid, a constituent of valerian root, has been found to act as a 5-HT_5A receptor agonist, and this action could be involved in the sleep-promoting effects of valerian.

5-HT₆ receptor agonists

No selective agonists of the 5-HT₆ receptor have been approved for medical use. Selective 5-HT₆ receptor agonists like E-6801, E-6837, EMDT, WAY-181,187, and WAY-208,466 show antidepressant, anxiolytic, antiobsessional, and appetite suppressant effects in animals, but also impair cognition and memory.^[18]

5-HT₇ receptor agonists

See also

References

1. ^http://adisinsight.springer.com/drugs/800000719
2. ^{{cite journal | vauthors = Capi M, de Andrés F, Lionetto L, Gentile G, Cipolla F, Negro A, Borro M, Martelletti P, Curto M | title = Lasmiditan for the treatment of migraine | journal = Expert Opin Investig Drugs | volume = 26 | issue = 2 | pages = 227–234 | year = 2017 | pmid = 28076702 | doi = 10.1080/13543784.2017.1280457 | url = }}
3. ^http://adisinsight.springer.com/drugs/800028519
4. ^{{cite journal|last=Aghajanian GK, Marek GJ|title=Serotonin and Hallucinogens|journal=Neuropharmacology|year=1999|volume=21|issue= 2S|pages=16S|doi=10.1016/s0893-133x(98)00135-3}}
5. ^{{cite journal | vauthors = Halberstadt AL | title = Pharmacology and Toxicology of N-Benzylphenethylamine ("NBOMe") Hallucinogens | journal = Curr Top Behav Neurosci | volume = 32 | issue = | pages = 283–311 | year = 2017 | pmid = 28097528 | doi = 10.1007/7854_2016_64 | url = }}
6. ^{{cite journal | vauthors = Lawn W, Barratt M, Williams M, Horne A, Winstock A | title = The NBOMe hallucinogenic drug series: Patterns of use, characteristics of users and self-reported effects in a large international sample | journal = J. Psychopharmacol. (Oxford) | volume = 28 | issue = 8 | pages = 780–8 | year = 2014 | pmid = 24569095 | doi = 10.1177/0269881114523866 | url = }}
7. ^¹²{{cite journal | vauthors = Wood DM, Sedefov R, Cunningham A, Dargan PI | title = Prevalence of use and acute toxicity associated with the use of NBOMe drugs | journal = Clin Toxicol | volume = 53 | issue = 2 | pages = 85–92 | year = 2015 | pmid = 25658166 | doi = 10.3109/15563650.2015.1004179 | url = }}
8. ^{{cite journal | vauthors = Juncosa JI, Hansen M, Bonner LA, Cueva JP, Maglathlin R, McCorvy JD, Marona-Lewicka D, Lill MA, Nichols DE | title = Extensive rigid analogue design maps the binding conformation of potent N-benzylphenethylamine 5-HT2A serotonin receptor agonist ligands | journal = ACS Chem Neurosci | volume = 4 | issue = 1 | pages = 96–109 | year = 2013 | pmid = 23336049 | pmc = 3547484 | doi = 10.1021/cn3000668 | url = }}
9. ^https://www.google.com/patents/US7655691
10. ^¹²³{{cite journal | vauthors = Suzuki J, Dekker MA, Valenti ES, Arbelo Cruz FA, Correa AM, Poklis JL, Poklis A | title = Toxicities associated with NBOMe ingestion-a novel class of potent hallucinogens: a review of the literature | journal = Psychosomatics | volume = 56 | issue = 2 | pages = 129–39 | year = 2015 | pmid = 25659919 | pmc = 4355190 | doi = 10.1016/j.psym.2014.11.002 | url = }}
11. ^{{cite journal | vauthors = Haberzettl R, Bert B, Fink H, Fox MA | title = Animal models of the serotonin syndrome: a systematic review | journal = Behav. Brain Res. | volume = 256 | issue = | pages = 328–45 | year = 2013 | pmid = 24004848 | doi = 10.1016/j.bbr.2013.08.045 | url = }}
12. ^{{cite journal | vauthors = Gillman PK | title = A review of serotonin toxicity data: implications for the mechanisms of antidepressant drug action | journal = Biol. Psychiatry | volume = 59 | issue = 11 | pages = 1046–51 | year = 2006 | pmid = 16460699 | doi = 10.1016/j.biopsych.2005.11.016 | url = }}
13. ^{{cite journal | vauthors = Iqbal MM, Basil MJ, Kaplan J, Iqbal MT | title = Overview of serotonin syndrome | journal = Ann Clin Psychiatry | volume = 24 | issue = 4 | pages = 310–8 | year = 2012 | pmid = 23145389 | doi = | url = }}
14. ^¹Hutcheson, J. D., Setola, V., Roth, B. L., & Merryman, W. D. (2011). Serotonin receptors and heart valve disease—it was meant 2B. Pharmacology & Therapeutics, 132(2), 146-157.
15. ^Brea, J., Castro-Palomino, J., Yeste, S., Cubero, E., Párraga, A., Domínguez, E., & Loza, M. I. (2010). Emerging Opportunities and Concerns for Drug Discovery at Serotonin 5-HT2B Receptors. Current Topics in Medicinal Chemistry, 10(5), 493-503.
16. ^Halberstadt, A. L., & Geyer, M. A. (2011). Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens. Neuropharmacology, 61(3), 364-381.
17. ^Zolkowska, D., Rothman, R. B., & Baumann, M. H. (2006). Amphetamine analogs increase plasma serotonin: implications for cardiac and pulmonary disease. Journal of Pharmacology and Experimental Therapeutics, 318(2), 604-610.
18. ^{{cite journal | vauthors = Karila D, Freret T, Bouet V, Boulouard M, Dallemagne P, Rochais C | title = Therapeutic Potential of 5-HT6 Receptor Agonists | journal = J. Med. Chem. | volume = 58 | issue = 20 | pages = 7901–12 | year = 2015 | pmid = 26099069 | doi = 10.1021/acs.jmedchem.5b00179 | url = }}

Non-selective agonists

5-HT1 receptor agonists

5-HT1A receptor agonists

5-HT1B receptor agonists

5-HT1D receptor agonists

5-HT1E receptor agonists

5-HT1F receptor agonists

5-HT2 receptor agonists

5-HT2A receptor agonists

5-HT2B receptor agonists

5-HT2C receptor agonists

5-HT3 receptor agonists

5-HT4 receptor agonists

5-HT5A receptor agonists

5-HT6 receptor agonists

5-HT7 receptor agonists