In Vitro Screening of Psychoactive Drugs by [35S]GTP.GAMMA.S Binding in Rat Brain Membranes

Nonaka, Ryouichi; Nagai, Fumiko; Ogata, Akio; Satoh, Kanako

doi:10.1248/bpb.30.2328

Cited by 29 publications

(18 citation statements)

References 22 publications

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“…However, a study using a fluorometric imaging plate reader technique in Chinese hamster ovary-K1 cells reported that racemic DOI had 61% the efficacy of 5-HT in this assay (Porter et al, 1999). A more recent study using an assay of nonspecific G protein activation in rat brain membranes reported that DPT was 46% as efficacious as 5-HT using these methods, which was identical to the relative efficacy obtained with the DOI analog 2,5-dimethoxy-4-iodophenethylamine (Nonaka et al, 2007). Thus, based on the available evidence, it is difficult to interpret the present results through the lens of intrinsic efficacy.…”

Section: Discussionmentioning

confidence: 59%

Tolerance and Cross-Tolerance to Head Twitch Behavior Elicited by Phenethylamine- and Tryptamine-Derived Hallucinogens in Mice

Smith

Bailey

Williams

et al. 2014

J Pharmacol Exp Ther

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The serotonin 5-hydroxytryptamine 2A (5-HT 2A ) receptor is a potential therapeutic target to a host of neuropsychiatric conditions, but agonist actions at this site are linked to abuse-related hallucinogenic effects that may limit therapeutic efficacy of chronic drug administration. Tolerance to some effects of hallucinogens has been observed in humans and laboratory animals, but the understanding of tolerance and cross-tolerance between distinct structural classes of hallucinogens is limited. Here, we used the drug-elicited head twitch response (HTR) in mice to assess the development of tolerance and cross-tolerance with two phenethylamine-derived [DOI (2,5-dimethoxy-4-iodoamphetamine) and 2C-T-7 (2,5-dimethoxy-4-propylthiophenethylamine)] and two tryptamine-derived [DPT (N,N-dipropyltryptamine) and DIPT (N, N-diisopropyltryptamine)] drugs with agonist affinity for 5-HT 2A receptors. Tolerance developed to HTR elicited by daily DOI or 2C-T-7, but not to HTR elicited by DPT or DIPT. DOI-elicited tolerance was not surmountable with dose, and a similar insurmountable cross-tolerance was evident when DOI-tolerant mice were tested with various doses of 2C-T-7 or DPT. These studies suggest that the use of phenethylamine-derived hallucinogens as therapeutic agents may be limited not only by their abuse potential, but also by the rapid development of tolerance that would likely be maintained even if a patient were switched to a different 5-HT 2A agonist medication from a distinct structural class. However, these experiments also imply that tryptamine-derived hallucinogens might have a reduced potential for tolerance development, compared with phenethylamine-derived 5-HT 2A agonists, and might therefore be more suitable for chronic administration in a therapeutic context.

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Section: Discussionmentioning

confidence: 59%

Tolerance and Cross-Tolerance to Head Twitch Behavior Elicited by Phenethylamine- and Tryptamine-Derived Hallucinogens in Mice

Smith

Bailey

Williams

et al. 2014

J Pharmacol Exp Ther

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“…The standard [ 35 S]GTPcS binding assays were carried out in a 96-well microplate according to the procedure of Mato et al [13] and Nonaka et al [14] with minor modifications. Briefly, the assay buffer consisted of 20 mM HEPES (pH 7.6), 7 mM MgCl 2 , 100 mM NaCl, 1 mM EDTA, 0.2 mM DTT, 10 lM DPCPX, and 0.1% (w/v) BSA.…”

Section: Membrane Preparationmentioning

confidence: 99%

Identification and quantitation of a benzoylindole (2-methoxyphenyl)(1-pentyl-1H-indol-3-yl)methanone and a naphthoylindole 1-(5-fluoropentyl-1H-indol-3-yl)-(naphthalene-1-yl)methanone (AM-2201) found in illegal products obtained via the Internet and their cannabimimetic effects evaluated by in vitro [35S]GTPγS binding assays

et al. 2011

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“…5-MeO-DALT binds 5-HT 1A , 2A, 2B and 2C receptors with high affinity, acting as a full agonist at these receptors (Nonaka et al, 2007; Arunotayanum et al, 2013; Cozzi & Daley, 2016). It also binds a range of other receptors, including adrenergic, D3, H1, H2, and sigma 1 and 2 receptors (Arunotayanum et al, 2013; Cozzi & Daley, 2016).…”

Section: Introductionmentioning

confidence: 99%

Locomotor and discriminative stimulus effects of four novel hallucinogens in rodents

Gatch

Dolan

Forster

2017

Behavioural Pharmacology

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There has been increasing use of novel synthetic hallucinogenic compounds, 25B-NBOMe, 25C-NBOMe, 25I-NBOMe, and 5-MeO-DALT, which have been associated with severe toxicities. These four compounds were tested for discriminative stimulus effects similar to a prototypical hallucinogen (−)-2,5-dimethoxy-4-methylamphetamine (DOM) and to the entactogen (±)-3,4-methylenedioxymethamphetamine (MDMA). Locomotor activity in mice was tested to obtain dose range and time course information. 25B-NBOMe, 25C-NBOMe and 25I-NBOMe decreased locomotor activity. 5-MeO-DALT dose-dependently increased locomotor activity with a peak at 10 mg/kg. A higher dose (25 mg/kg) suppressed activity. 25B-NBOMe fully substituted (≥80%) in both DOM- and MDMA-trained rats at 0.5 mg/kg. However, higher doses produced much lower levels of drug-appropriate responding in both DOM- and MDMA-trained rats. 25C-NBOMe fully substituted in DOM-trained rats, but produced only 67% drug-appropriate responding in MDMA-trained rats at doses that suppressed responding. 25I-NBOMe produced 74 to 78% drug-appropriate responding in DOM- and MDMA-trained rats at doses that suppressed responding. 5-MeO-DALT fully substituted for DOM, but produced little few or no MDMA-like effects. All of the compounds but except 25I-NBOMe produced fully substituted for DOM, whereas only 25B-NBOMe fully substituted for MDMA. However, the failure of 25I-NBOMe to fully substitute for either MDMA or DOM was more likely due to its substantial rate rate-depressant effects than to weak discriminative stimulus effects. All of the compounds are likely to attract recreational users for their hallucinogenic properties, but likely probably much less interest as substitutes for MDMA. Although no acute adverse effects were observed at the doses tested, the substantial toxicities reported in humans, coupled with the high likelihood for illicit use, suggests that these compounds have the same potential for abuse as other, currently scheduled compounds.

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In Vitro Screening of Psychoactive Drugs by [35S]GTP.GAMMA.S Binding in Rat Brain Membranes

Abstract: We constructed a reproducible, simple, and small-scale determination method of the psychoactive drugs that acted directly on the monoamine receptor by measuring the activation of [

Cited by 29 publications

References 22 publications

Tolerance and Cross-Tolerance to Head Twitch Behavior Elicited by Phenethylamine- and Tryptamine-Derived Hallucinogens in Mice

Tolerance and Cross-Tolerance to Head Twitch Behavior Elicited by Phenethylamine- and Tryptamine-Derived Hallucinogens in Mice

Locomotor and discriminative stimulus effects of four novel hallucinogens in rodents

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