Role of 5-HT1A- and 5-HT2A receptors for the murine model of the serotonin syndrome

Haberzettl, Robert; Fink, Heidrun; Bert, Bettina

doi:10.1016/j.vascn.2014.07.003

Cited by 30 publications

(11 citation statements)

References 41 publications

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“…SSR were determined as not present (=0) or present (=1) during each observation session, for a total score of between 0 and 6. SSR scored in this manner included flat body posture, forepaw treading, grooming, head weaving, hind limb abduction, moon walking, piloerection, Straub tail, and tremor, as previously described 67 . In addition, the total number of HTR and rears displayed across all six observation sessions were also tallied.…”

Section: Test Of (+)-5-fpt To Elicit Serotonin Syndromementioning

confidence: 99%

An Orally Active Phenylaminotetralin-Chemotype Serotonin 5-HT₇ and 5-HT_1A Receptor Partial Agonist That Corrects Motor Stereotypy in Mouse Models

Canal

Felsing

Liu

et al. 2015

ACS Chem. Neurosci.

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Stereotypy (e.g., repetitive hand waving) is a key phenotype of autism spectrum disorder, Fragile X and Rett syndromes, and other neuropsychiatric disorders, and its severity correlates with cognitive and attention deficits. There are no effective treatments, however, for stereotypy. Perturbation of serotonin (5-HT) neurotransmission contributes to stereotypy, suggesting that distinct 5-HT receptors may be pharmacotherapeutic targets to treat stereotypy and related neuropsychiatric symptoms. For example, preclinical studies indicate that 5-HT7 receptor activation corrects deficits in mouse models of Fragile X and Rett syndromes, and clinical trials for autism are underway with buspirone, a 5-HT1A partial agonist with relevant affinity at 5-HT7 receptors. Herein, we report the synthesis, in vitro molecular pharmacology, behavioral pharmacology, and pharmacokinetic parameters in mice after subcutaneous and oral administration of (+)-5-(2'-fluorophenyl)-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine ((+)-5-FPT), a new, dual partial agonist targeting both 5-HT7 (Ki = 5.8 nM, EC50 = 34 nM) and 5-HT1A (Ki = 22 nM, EC50 = 40 nM) receptors. Three unique, heterogeneous mouse models were used to assess the efficacy of (+)-5-FPT to reduce stereotypy: idiopathic jumping in C58/J mice, repetitive body rotations in C57BL/6J mice treated with the NMDA antagonist, MK-801, and repetitive head twitching in C57BL/6J mice treated with the 5-HT2 agonist, DOI. Systemic (+)-5-FPT potently and efficaciously reduced or eliminated stereotypy in each of the mouse models without altering locomotor behavior on its own, and additional tests showed that (+)-5-FPT, at the highest behaviorally active dose tested, enhanced social interaction and did not cause behaviors indicative of serotonin syndrome. These data suggest that (+)-5-FPT is a promising medication for treating stereotypy in psychiatric disorders.

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Section: Test Of (+)-5-fpt To Elicit Serotonin Syndromementioning

confidence: 99%

An Orally Active Phenylaminotetralin-Chemotype Serotonin 5-HT₇ and 5-HT_1A Receptor Partial Agonist That Corrects Motor Stereotypy in Mouse Models

Canal

Felsing

Liu

et al. 2015

ACS Chem. Neurosci.

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“…Among serotonin receptors, post-synaptic 5-HT 1A and 5-HT 2A receptors have been suggested to be importantly involved in serotonin syndrome [14,34]. Consistently, it has been reported that the specific 5-HT 1A receptor agonist 8-OH-DPAT or the specific 5-HT 2A receptor agonist (4-Bromo-3,6-dimethoxybenzocyclobuten-1-yl)methylamine hydrobromide TCB-2 induces serotonin syndrome behavior in mice [35][36][37]. In most cells and tissues, 5-HT receptors activate phospholipase C, which causes stimulation of protein kinase C (PKC) [38].…”

Section: Introductionmentioning

confidence: 78%

Ginsenoside Re Protects against Serotonergic Behaviors Evoked by 2,5-Dimethoxy-4-iodo-amphetamine in Mice via Inhibition of PKCδ-Mediated Mitochondrial Dysfunction

Shin

Jeong

Nguyen

et al. 2021

IJMS

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It has been recognized that serotonin 2A receptor (5-HT2A) agonist 2,5-dimethoxy-4-iodo-amphetamine (DOI) impairs serotonergic homeostasis. However, the mechanism of DOI-induced serotonergic behaviors remains to be explored. Moreover, little is known about therapeutic interventions against serotonin syndrome, although evidence suggests that ginseng might possess modulating effects on the serotonin system. As ginsenoside Re (GRe) is well-known as a novel antioxidant in the nervous system, we investigated whether GRe modulates 5-HT2A receptor agonist DOI-induced serotonin impairments. We proposed that protein kinase Cδ (PKCδ) mediates serotonergic impairments. Treatment with GRe or 5-HT2A receptor antagonist MDL11939 significantly attenuated DOI-induced serotonergic behaviors (i.e., overall serotonergic syndrome behaviors, head twitch response, hyperthermia) by inhibiting mitochondrial translocation of PKCδ, reducing mitochondrial glutathione peroxidase activity, mitochondrial dysfunction, and mitochondrial oxidative stress in wild-type mice. These attenuations were in line with those observed upon PKCδ inhibition (i.e., pharmacologic inhibitor rottlerin or PKCδ knockout mice). Furthermore, GRe was not further implicated in attenuation mediated by PKCδ knockout in mice. Our results suggest that PKCδ is a therapeutic target for GRe against serotonergic behaviors induced by DOI.

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“…Beyin sapı ve spinal kordaki 5-HT1A ve 5-HT2 reseptörlerinin aşırı uyarılması sonucu artan serotonerjik nörotransmisyonun serotonin sendromu gelişiminden sorumlu olduğu düşünül-mektedir (2,3) .…”

Section: Discussionunclassified

Serious Drug Reaction: Serotonin Syndrome

Koçak¹,

Yarar²,

Çarman³

et al. 2015

IKSST

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ÖZ İKSST Derg 7(3):144-146, 2015 doi:10.5222/iksst.2015 GİRİş Serotonin sendromu nadir görülen, mortalite riski bulunan serotonerjik etkili ilaçların tedavi edici dozda veya aşırı miktarda alınmasından ya da serotonerjik etkili iki ilacın farmakolojik etkileşiminden kaynaklanan bir ilaç reaksiyonudur. Genellikle hekimler tarafından özellikle hasta semptomlarının hafif olduğu durumlarda akla gelmeyen ve atlanan bir hastalıktır. Geniş bir semptom yelpazesi vardır. Görülen bulgular tremor, diyare ve hipertansiyon şeklinde nispeten hafif olabileceği gibi ağır olgular rijidite, hipertermi, çoklu organ yetmezliği ve ölümle de sonuçlanabilir. Hafif semptom ve bulgularla seyreden olgular için serotonin toksisitesi terimi de kullanılmaktadır (1) . Biz burada serotonerjik etkili iki ilacı kombine kullanan ve serotonin sendromu gelişen bir hastamızı sunmak istedik. oLGUOn altı yaşında erkek hasta çocuk nöroloji polikliniğine jeneralize tonik klonik tarzda nöbet geçirme yakınması ile başvurdu. Daha önce nöbet öyküsü olmayan hastanın son bir aydır çocuk psikiyatrisi tarafından obsesif kompulsif bozukluk tanısı ile baş-lanan fluoksetin (20 mg/gün), aripiprazol (10 mg/ gün) ve imipramin hidroklorür (50 mg/gün) tedavilerini aldığı öğrenildi. Hastanın tedavi başlandıktan sonra huzursuz olduğu, aşırı sinirlenme, bağırma, bazen ağlama şeklinde davranışlarının olduğu öğre-nildi. Fizik muayenesinde hiperhidrozisi dikkat çeken hastanın ateş 39°C, tansiyon 150/60 mmHg, nabız 116/dk. olarak saptandı. Özellikle alt extremitelerde tonus artışı ve derin tendon reflekslerinde artış ile birlikte ellerinde belirgin tremoru mevcuttu. Laboratuvar tetkiklerinde, kan gazında pH: 7,062, pCO 2 : 41,3 mmHg HCO 3 : 10,9 mmol/L, baz açığı -19 mmol/L, CK: 599 U/L saptandı. Hastanın elektroensefalogram (EEG) ve beyin MRG çalışmaları normal sonuçlandı. Hastada mevcut bulgularla serotonin sendromu düşünüldü. Monitorize edilen hastanın fluoksetin ve imipramin tedavileri kesildi. Hastanın kliniğinde 24 saat içerisinde belirgin düzelme oldu. Metabolik asidozla birlikte hiperhidrozisi ve hipertansif değerleri giderek düzelen hastanın üç günlük

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Role of 5-HT1A- and 5-HT2A receptors for the murine model of the serotonin syndrome

Cited by 30 publications

References 41 publications

An Orally Active Phenylaminotetralin-Chemotype Serotonin 5-HT₇ and 5-HT_1A Receptor Partial Agonist That Corrects Motor Stereotypy in Mouse Models

An Orally Active Phenylaminotetralin-Chemotype Serotonin 5-HT₇ and 5-HT_1A Receptor Partial Agonist That Corrects Motor Stereotypy in Mouse Models

Ginsenoside Re Protects against Serotonergic Behaviors Evoked by 2,5-Dimethoxy-4-iodo-amphetamine in Mice via Inhibition of PKCδ-Mediated Mitochondrial Dysfunction

Serious Drug Reaction: Serotonin Syndrome

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Role of 5-HT1A- and 5-HT2A receptors for the murine model of the serotonin syndrome

Cited by 30 publications

References 41 publications

An Orally Active Phenylaminotetralin-Chemotype Serotonin 5-HT7 and 5-HT1A Receptor Partial Agonist That Corrects Motor Stereotypy in Mouse Models

An Orally Active Phenylaminotetralin-Chemotype Serotonin 5-HT7 and 5-HT1A Receptor Partial Agonist That Corrects Motor Stereotypy in Mouse Models

Ginsenoside Re Protects against Serotonergic Behaviors Evoked by 2,5-Dimethoxy-4-iodo-amphetamine in Mice via Inhibition of PKCδ-Mediated Mitochondrial Dysfunction

Serious Drug Reaction: Serotonin Syndrome

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Product

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An Orally Active Phenylaminotetralin-Chemotype Serotonin 5-HT₇ and 5-HT_1A Receptor Partial Agonist That Corrects Motor Stereotypy in Mouse Models

An Orally Active Phenylaminotetralin-Chemotype Serotonin 5-HT₇ and 5-HT_1A Receptor Partial Agonist That Corrects Motor Stereotypy in Mouse Models