5-Methoxy-α-methyltryptamine (5-MeO-AMT), a tryptamine derivative, induces head-twitch responses in mice through the activation of serotonin receptor 2a in the prefrontal cortex

Abiero, Arvie; Botanas, Chrislean Jun; Sayson, Leandro Val; Custodio, Raly James Perez; Peña, June Bryan de la; Kim, Mi-Kyung; Lee, Hyun Jun; Seo, Joung‐Wook; Ryu, In Soo; Chang, Cho Min; Yang, Jae-Seung; Lee, Yong Sup; Jang, Choon‐Gon; Kim, Hee Jin; Cheong, Jae Hoon

doi:10.1016/j.bbr.2018.07.020

Cited by 13 publications

(20 citation statements)

References 53 publications

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“…PYT HCl, PIT HCl, DBT HCl, KS, and METH were diluted with normal saline. All drugs were administered either intraperitoneally (open field test [OFT], CPP and HTR) or intravenously (SA), and the doses were based on prior experiments that addressed abuse potential and tryptamine induced-HTR (Darmani et al ., 1990b; Fantegrossi et al ., 2010; Gatch et al ., 2011; Canal and Morgan, 2012; Creehan et al ., 2015; Botanas et al ., 2017; Abiero et al ., 2019).…”

Section: Methodsmentioning

confidence: 99%

“…The HTR is a distinct twitching behavior of the head of rodents. The HTR procedure followed that described by our previous study (Abiero et al ., 2019). It is easily monitored and usually cannot be mistaken for other head movements such as head-shakes or head-jerks.…”

Section: Methodsmentioning

confidence: 99%

“…with vehicle, PYT HCl, PIT HCl, DBT HCl and 2-MT HCl (3 mg/kg) once a day for 7 days and challenged with the same drug and dose following 7 days of drug abstinence. A dose of 3mg/kg was selected for the present study because in a previous study it had submaximal effects and reliably increased the number of head twitches (Abiero et al ., 2019). To determine the involvement of 5-HTR2a, another cohorts of mice (n=6 per group) were injected with KS (0.1 mg/kg) 10 min before PYT HCl, PIT HCl, DBT HCl, and 2-MT HCl (3 mg/kg) or veh administration and were observed for the HTR.…”

Section: Methodsmentioning

confidence: 99%

“…The HTR is a brief paroxysmal head rotation in rodents that is thought to be mediated via the 5-HT2a receptor (Corne et al ., 1963; Corne and Pickering, 1967; Canal and Morgan, 2012). Tryptamine hallucinogens and 5-HTR2a agonists like 5-MeO-DIPT, 5-MeO-AMT, and 5-MeO-DMT have been reported to elicit head twitches in rodents (Fantegrossi et al ., 2006; Halberstadt et al ., 2011; Abiero et al ., 2019). Pretreatment with 5-HTR2a antagonists, such as ketanserin (KS), block the drug-induced HTR (Fantegrossi et al ., 2010).…”

Section: Introductionmentioning

confidence: 99%

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Four Novel Synthetic Tryptamine Analogs Induce Head-Twitch Responses and Increase 5-HTR2a in the Prefrontal Cortex in Mice

Abiero

Ryu

Botanas

et al. 2020

Biomolecules & Therapeutics

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Tryptamines are monoamine alkaloids with hallucinogenic properties and are widely abused worldwide. To hasten the regulations of novel substances and predict their abuse potential, we designed and synthesized four novel synthetic tryptamine analogs: Pyrrolidino tryptamine hydrochloride (PYT HCl), Piperidino tryptamine hydrochloride (PIT HCl), N,N-dibutyl tryptamine hydrochloride (DBT HCl), and 2-Methyl tryptamine hydrochloride (2-MT HCl). Then, we evaluated their rewarding and reinforcing effects using the conditioned place preference (CPP) and self-administration (SA) paradigms. We conducted an open field test (OFT) to determine the effects of the novel compounds on locomotor activity. A head-twitch response (HTR) was also performed to characterize their hallucinogenic properties. Lastly, we examined the effects of the compounds on 5-HTR1a and 5-HTR2a in the prefrontal cortex using a quantitative real-time polymerase chain reaction (qRT-PCR) assay. None of the compounds induced CPP in mice or initiated SA in rats. PYT HCl and PIT HCl reduced the locomotor activity and elevated the 5-HTR1a mRNA levels in mice. Acute and repeated treatment with the novel tryptamines elicited HTR in mice. Furthermore, a drug challenge involving a 7-day abstinence from drug use produced higher HTR than acute and repeated treatments. Both the acute treatment and drug challenge increased the 5-HTR2a mRNA levels. Ketanserin blocked the induced HTR. Taken together, the findings suggest that PYT HCl, PIT HCl, DBT HCl, and 2-MT HCl produce hallucinogenic effects via 5-HTR2a stimulation, but may have low abuse potential.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Four Novel Synthetic Tryptamine Analogs Induce Head-Twitch Responses and Increase 5-HTR2a in the Prefrontal Cortex in Mice

Abiero

Ryu

Botanas

et al. 2020

Biomolecules & Therapeutics

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“…On the other hand, the van der Waals interaction between Phe-339 and N-benzyl ring of NBOMes and the hydrogen bond formed by Tyr-370 with the 2-position oxygen on this ring are considered to play a key role in the high potency and affinity of these compounds binding to 5-HT 2A receptor (Silva et al, 2011;Ísberg et al, 2011). The activation of cortical 5-HT 2A receptors induces the head twitch response (HTR) in mice and rats, also referred to as wet dog shakes (Willins and Meltzer, 1997;Abiero et al, 2019). The HTR is widely used as a behavioral marker for hallucinogen effects in humans (Halberstadt and Geyer, 2018).…”

Section: Pharmacology Of Nbomesmentioning

confidence: 99%

NBOMes–Highly Potent and Toxic Alternatives of LSD

2020

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Recently, a new class of psychedelic compounds named NBOMe (or 25X-NBOMe) has appeared on the illegal drug market. NBOMes are analogs of the 2C family of phenethylamine drugs, originally synthesized by Alexander Shulgin, that contain a N-(2-methoxy)benzyl substituent. The most frequently reported drugs from this group are 25I-NBOMe, 25B-NBOMe, and 25C-NBOMe. NBOMe compounds are ultrapotent and highly efficacious agonists of serotonin 5-HT 2A and 5-HT 2C receptors (Ki values in low nanomolar range) with more than 1000-fold selectivity for 5-HT 2A compared with 5-HT 1A. They display higher affinity for 5-HT 2A receptors than their 2C counterparts and have markedly lower affinity, potency, and efficacy at the 5-HT 2B receptor compared to 5-HT 2A or 5-HT 2C. The drugs are sold as blotter papers, or in powder, liquid, or tablet form, and they are administered sublingually/buccally, intravenously, via nasal insufflations, or by smoking. Since their introduction in the early 2010s, numerous reports have been published on clinical intoxications and fatalities resulting from the consumption of NBOMe compounds. Commonly observed adverse effects include visual and auditory hallucinations, confusion, anxiety, panic and fear, agitation, uncontrollable violent behavior, seizures, excited delirium, and sympathomimetic signs such mydriasis, tachycardia, hypertension, hyperthermia, and diaphoresis. Rhabdomyolysis, disseminated intravascular coagulation, hypoglycemia, metabolic acidosis, and multiorgan failure were also reported. This survey provides an updated overview of the pharmacological properties, pattern of use, metabolism, and desired effects associated with NBOMe use. Special emphasis is given to cases of nonfatal and lethal intoxication involving these compounds. As the analysis of NBOMes in biological materials can be challenging even for laboratories applying modern sensitive techniques, this paper also presents the analytical methods most commonly used for detection and identification of NBOMes and their metabolites.

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Preparation, spectroscopic study of Schiff base derived from dopamine and metal Ni(II), Pd(II), and Pt(IV) complexes, and activity determination as antioxidants

Kareem

Al‐Hamdani

Jirjees

et al. 2020

J of Physical Organic Chem

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A new Schiff base (HL2) ligand (4‐{2‐[(2‐hydroxy‐benzylidene)‐amino]‐ethyl}‐benzene‐1,2‐diol) has been synthesized by condensing of 4‐(2‐amino‐ethyl)‐benzene‐1,2‐diol and 2‐hydroxy‐benzaldehyde. In turn, its transition metal complexes were prepared, having the following general formulas: Ni(L2)2, Pd(L2)2, and Pt(L2)22Cl. The prepared ligand and its metal complexes Ni(II), Pd(II), and Pt(IV) have been characterized by Fourier transform infrared (FTIR) spectra, proton nuclear magnetic resonance (1H‐NMR) elemental analysis, metal content, chloride content, molar conductance, ultraviolet–visible (UV–Vis) spectra, magnetic susceptibility, mass spectrometry (MS) spectra, and thermogravimetric analysis (TGA). The consequences proposed that Schiff base acts like a bidentate ligand for all the prepared complexes. The antioxidant performance of as‐prepared compounds was inspected using the DPPH radical scavenging method. The compounds showed antioxidant activities of scavenging free radicals.

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5-Methoxy-α-methyltryptamine (5-MeO-AMT), a tryptamine derivative, induces head-twitch responses in mice through the activation of serotonin receptor 2a in the prefrontal cortex

Cited by 13 publications

References 53 publications

Four Novel Synthetic Tryptamine Analogs Induce Head-Twitch Responses and Increase 5-HTR2a in the Prefrontal Cortex in Mice

Four Novel Synthetic Tryptamine Analogs Induce Head-Twitch Responses and Increase 5-HTR2a in the Prefrontal Cortex in Mice

NBOMes–Highly Potent and Toxic Alternatives of LSD

Preparation, spectroscopic study of Schiff base derived from dopamine and metal Ni(II), Pd(II), and Pt(IV) complexes, and activity determination as antioxidants

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