:MK-212

MK-212 is an agonist of the serotonin 5-HT₂ receptors, including the serotonin 5-HT_2C, 5-HT_2B, and 5-HT_2A receptors, in that order of potency.{{cite journal | vauthors = Porter RH, Benwell KR, Lamb H, Malcolm CS, Allen NH, Revell DF, Adams DR, Sheardown MJ | title = Functional characterization of agonists at recombinant human 5-HT2A, 5-HT2B and 5-HT2C receptors in CHO-K1 cells | journal = Br J Pharmacol | volume = 128 | issue = 1 | pages = 13–20 | date = September 1999 | pmid = 10498829 | pmc = 1571597 | doi = 10.1038/sj.bjp.0702751 | url = }}{{cite journal | vauthors = Acuña-Castillo C, Villalobos C, Moya PR, Sáez P, Cassels BK, Huidobro-Toro JP | title = Differences in potency and efficacy of a series of phenylisopropylamine/phenylethylamine pairs at 5-HT(2A) and 5-HT(2C) receptors | journal = Br J Pharmacol | volume = 136 | issue = 4 | pages = 510–519 | date = June 2002 | pmid = 12055129 | pmc = 1573376 | doi = 10.1038/sj.bjp.0704747 | url = https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1038/sj.bjp.0704747}}{{cite journal | vauthors = Vickers SP, Easton N, Malcolm CS, Allen NH, Porter RH, Bickerdike MJ, Kennett GA | title = Modulation of 5-HT(2A) receptor-mediated head-twitch behaviour in the rat by 5-HT(2C) receptor agonists | journal = Pharmacol Biochem Behav | volume = 69 | issue = 3-4 | pages = 643–652 | date = 2001 | pmid = 11509227 | doi = 10.1016/s0091-3057(01)00552-4 | url = }} It is a full agonist of the serotonin 5-HT_2C receptor, a moderate-efficacy partial agonist of the serotonin 5-HT_2B receptor, and a partial to full agonist of the serotonin 5-HT_2A receptor. The drug shows similar potency in activating the serotonin 5-HT_2C and 5-HT_2B receptors and around 10- to 30-fold lower relative potency in activating the serotonin 5-HT_2A receptor. It also shows low affinity for the serotonin 5-HT_1A and 5-HT_1B receptors.{{cite journal | vauthors = Hoyer D | title = Functional correlates of serotonin 5-HT1 recognition sites | journal = J Recept Res | volume = 8 | issue = 1-4 | pages = 59–81 | date = 1988 | pmid = 3290473 | doi = 10.3109/10799898809048978 | url = }}

In a 1977 study by Clineschidt and colleagues, they dosed mice with varying concentrations of MK-212, and observed its effects.{{cite journal | vauthors = Clineschmidt BV, Mcguffin JC, Pflueger AB | title = Central serotonin-like activity of 6-chloro-2-[1-piperazinyl]-pyrazine (CPP; MK-212) | journal = European Journal of Pharmacology | volume = 44 | issue = 1 | pages = 65–74 | date = July 1977 | pmid = 885160 | doi = 10.1016/0014-2999(77)90117-0 }}

The result correlated very well to binding of indolealkylamine receptors, such as the serotonin and tryptamine receptors, which shows four characteristics. Namely, increased frequency of muscle twitching, increased twitching of the head, "an increase in the strength of the crossed extensor reflex in the acutely spinalized rat", and the cause of complex motor syndrome.

MK-212 did not produce hallucinogenic effects in humans at doses of up to 40{{nbsp}}mg orally.{{cite journal | vauthors = Lowy MT, Meltzer HY | title = Stimulation of serum cortisol and prolactin secretion in humans by MK-212, a centrally active serotonin agonist | journal = Biol Psychiatry | volume = 23 | issue = 8 | pages = 818–828 | date = April 1988 | pmid = 3365458 | doi = 10.1016/0006-3223(88)90070-4 | url = | quote = The effects of MK-212 [6-chloro-2-(1-piperazinyl)-pyrazine] (10, 20, and 40 mg, orally), a centrally acting serotonin (5-HT) receptor agonist and placebo, on serum cortisol, prolactin, and growth hormone levels were studied in eight healthy men over 3-hr. [...] MK-212 was generally well tolerated by the subjects. Headache and nausea were observed at the higher doses, [...] It has been suggested that 5-HT2 receptor mechanisms may be involved in the mechanism of action of hallucinogenic agents (Glennon et al. 1984). None of the subjects reported hallucinations following any dose of MK-212. Interestingly, on occasion, alcoholic patients given a 20-mg dose of MK-212 have reported that MK-212 produces an LSD-like effect (Meltzer et al. unpublished observations). However, in rats trained to discriminate MK-212 from saline, LSD did not completely substitute for MK-212 (Cunningham et al. 1986). In addition, ketanserin failed to block the discriminative stimulus properties of MK-212.}} However, in other research, it occasionally produced LSD-like effects in alcoholic patients at a dose of 20{{nbsp}}mg. In addition, subsequent studies found that MK-212 at 20{{nbsp}}mg significantly increased ratings of feeling high and feeling strange.{{cite journal | vauthors = Lee HS, Bastani B, Friedman L, Ramirez L, Meltzer HY | title = Effect of the serotonin agonist, MK-212, on body temperature in schizophrenia | journal = Biol Psychiatry | volume = 31 | issue = 5 | pages = 460–470 | date = March 1992 | pmid = 1581424 | doi = 10.1016/0006-3223(92)90258-2 | url = }}{{cite journal | vauthors = Friedman L, Jesberger JA, Meltzer HY | title = The effect of apomorphine, MK-212 (6-chloro-2-[1-piperazinyl]-pyrazine) and placebo on smooth pursuit gain and corrective saccades in normal subjects | journal = Neuropsychopharmacology | volume = 11 | issue = 1 | pages = 49–62 | date = August 1994 | pmid = 7945744 | doi = 10.1038/npp.1994.35 | url = }}

• 2C-B-PP
• mCPP
• ORG-12962
• Quipazine

{{Reflist}}

{{Psychedelics}}

{{Serotonin receptor modulators}}

{{Piperazines}}

Category:5-HT2A agonists

Category:5-HT2B agonists

Category:5-HT2C agonists

Category:Chloroarenes

Category:1-Piperazinyl compounds

Category:Psychedelic arylpiperazines

Category:Pyrazines

Category:Serotonin receptor agonists