MK-212
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| Preferred IUPAC name
2-Chloro-6-(piperazin-1-yl)pyrazine | |
| Other names
CPP
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3D model (JSmol)
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CompTox Dashboard (EPA)
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| Properties | |
| C8H11ClN4 | |
| Molar mass | 198.65 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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MK-212, also known as 6-chloro-2-(1-piperazinyl)pyrazine (CPP), is a serotonin receptor agonist of the arylpiperazine family.[1][2] It is specifically described as a non-selective serotonin 5-HT2 receptor agonist[3] or as a "relatively selective serotonin 5-HT2C receptor full agonist.[4] The drug promotes the secretion of serum prolactin and cortisol in humans.[5]
Pharmacology
[edit]MK-212 is an agonist of the serotonin 5-HT2 receptors, including the serotonin 5-HT2C, 5-HT2B, and 5-HT2A receptors, in that order of potency.[6][7][8] It is a full agonist of the serotonin 5-HT2C receptor, a moderate-efficacy partial agonist of the serotonin 5-HT2B receptor, and a partial to full agonist of the serotonin 5-HT2A receptor.[6][7][8] The drug shows similar potency in activating the serotonin 5-HT2C and 5-HT2B receptors and around 10- to 30-fold lower relative potency in activating the serotonin 5-HT2A receptor.[6][7][8] It also shows low affinity for the serotonin 5-HT1A and 5-HT1B receptors.[9]
In a 1977 study by Clineschidt and colleagues, they dosed mice with varying concentrations of MK-212, and observed its effects.[10] 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,[6] "an increase in the strength of the crossed extensor reflex in the acutely spinalized rat", and the cause of complex motor syndrome.[10]
MK-212 did not produce hallucinogenic effects in humans at doses of up to 40 mg orally.[5] However, in other research, it occasionally produced LSD-like effects in alcoholic patients at a dose of 20 mg.[5] In addition, subsequent studies found that MK-212 at 20 mg significantly increased ratings of feeling high and feeling strange.[2][11][12]
See also
[edit]References
[edit]- ^ Clineschidmt BV (1979). "MK-212: a serotonin-like agonist in the CNS". General Pharmacology. 10 (4): 287–290. doi:10.1016/0306-3623(79)90054-5. PMID 488663.
- ^ a b Bastani B, Nash JF, Meltzer HY (September 1990). "Prolactin and cortisol responses to MK-212, a serotonin agonist, in obsessive-compulsive disorder". Archives of General Psychiatry. 47 (9): 833–839. doi:10.1001/archpsyc.1990.01810210041006. PMID 2203327.
- ^ Isaac M (2005). "Serotonergic 5-HT2C receptors as a potential therapeutic target for the design antiepileptic drugs". Curr Top Med Chem. 5 (1): 59–67. doi:10.2174/1568026053386980. PMID 15638778.
- ^ Walker EA, Kohut SJ, Hass RW, Brown EK, Prabandham A, Lefever T (December 2005). "Selective and nonselective serotonin antagonists block the aversive stimulus properties of MK212 and m-chlorophenylpiperazine (mCPP) in mice". Neuropharmacology. 49 (8): 1210–1219. doi:10.1016/j.neuropharm.2005.07.015. PMID 16165167.
- ^ a b c Lowy MT, Meltzer HY (April 1988). "Stimulation of serum cortisol and prolactin secretion in humans by MK-212, a centrally active serotonin agonist". Biol Psychiatry. 23 (8): 818–828. doi:10.1016/0006-3223(88)90070-4. PMID 3365458.
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.
- ^ a b c d Porter RH, Benwell KR, Lamb H, Malcolm CS, Allen NH, Revell DF, Adams DR, Sheardown MJ (September 1999). "Functional characterization of agonists at recombinant human 5-HT2A, 5-HT2B and 5-HT2C receptors in CHO-K1 cells". Br J Pharmacol. 128 (1): 13–20. doi:10.1038/sj.bjp.0702751. PMC 1571597. PMID 10498829.
- ^ a b c Acuña-Castillo C, Villalobos C, Moya PR, Sáez P, Cassels BK, Huidobro-Toro JP (June 2002). "Differences in potency and efficacy of a series of phenylisopropylamine/phenylethylamine pairs at 5-HT(2A) and 5-HT(2C) receptors". Br J Pharmacol. 136 (4): 510–519. doi:10.1038/sj.bjp.0704747. PMC 1573376. PMID 12055129.
- ^ a b c Vickers SP, Easton N, Malcolm CS, Allen NH, Porter RH, Bickerdike MJ, Kennett GA (2001). "Modulation of 5-HT(2A) receptor-mediated head-twitch behaviour in the rat by 5-HT(2C) receptor agonists". Pharmacol Biochem Behav. 69 (3–4): 643–652. doi:10.1016/s0091-3057(01)00552-4. PMID 11509227.
- ^ Hoyer D (1988). "Functional correlates of serotonin 5-HT1 recognition sites". J Recept Res. 8 (1–4): 59–81. doi:10.3109/10799898809048978. PMID 3290473.
- ^ a b Clineschmidt BV, Mcguffin JC, Pflueger AB (July 1977). "Central serotonin-like activity of 6-chloro-2-[1-piperazinyl]-pyrazine (CPP; MK-212)". European Journal of Pharmacology. 44 (1): 65–74. doi:10.1016/0014-2999(77)90117-0. PMID 885160.
- ^ Lee HS, Bastani B, Friedman L, Ramirez L, Meltzer HY (March 1992). "Effect of the serotonin agonist, MK-212, on body temperature in schizophrenia". Biol Psychiatry. 31 (5): 460–470. doi:10.1016/0006-3223(92)90258-2. PMID 1581424.
- ^ Friedman L, Jesberger JA, Meltzer HY (August 1994). "The effect of apomorphine, MK-212 (6-chloro-2-[1-piperazinyl]-pyrazine) and placebo on smooth pursuit gain and corrective saccades in normal subjects". Neuropsychopharmacology. 11 (1): 49–62. doi:10.1038/npp.1994.35. PMID 7945744.