In Vitro Screening of Psychoactive Drugs by [35S]GTP.GAMMA.S Binding in Rat Brain Membranes
Ryouichi Nonaka, Fumiko Nagai, Akio Ogata, Kanako Satoh
Biological and Pharmaceutical Bulletin 2007 DOI: 10.1248/bpb.30.2328 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rat brain membranes (striatal and cortical) |
| Interventions | 2C-C 2C-E 2C-I 5-MeO-DMT 5-MeO-DALT 5-MeO-AMT 5-MeO-MIPT 5-MeO-DIPT DPT AMT |
| Topics | Serotonin |
| Keywords | Phenethylamines Monoamine neurotransmitter Tryptamines Dopamine Gtp' Pharmacology G protein 5-HT Receptor |
| Citations | 31 |
| Key findings | Among 12 phenethylamines, only 2C-C, 2C-E, and 2C-I stimulated G protein binding, while all 7 tryptamines tested stimulated binding with 5-MeO-DMT being the most potent. |
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 [(35)S]guanosine-5'-O-(3-thio)-triphosphate binding to guanine nucleotide-binding proteins (G proteins). This method can simultaneously measure the effects of three monoamines, namely dopamine (DA), serotonin (5-HT), and norepinephrine (NE), in rat brain membranes using a 96-well microplate. Activation of D(1) and D(2) receptors in striatal membranes by DA as well as 5-HT and NEalpha(2) receptors in cortical membranes could be measured. Of 12 tested phenethylamines, 2,5-dimethoxy-4-chlorophenethylamine (2C-C), 2,5-dimethoxy-4-ethylphenethylamine (2C-E), and 2,5-dimethoxy-4-iodophenethylamine (2C-I) stimulated G protein binding. The other phenethylamines did not affect G protein binding. All 7 tryptamines tested stimulated G protein binding with the following rank order of potency; 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT)>5-methoxy-N,N-diallyltryptamine (5-MeO-DALT)>5-methoxy-alpha-methyltryptamine (5-MeO-AMT)>or=5-methoxy-N,N-methylisopropyltryptamine (5-MeO-MIPT)>5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT)>N,N-dipropyltryptamine (DPT)>or=alpha-methyltryptamine (AMT). This assay system was able to designate psychoactive drugs as prohibited substances in accordance with criteria set forth by the Tokyo Metropolitan government.