MK-212

Pharmacodynamics

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.^[8][9][10] 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.^[8][9][10] 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.^[8][9][10] It also shows low affinity for the serotonin 5-HT_1A and 5-HT_1B receptors.^[11] The comprehensive receptor interactions of MK-212 have been studied.^[12]

In a 1977 study by Clineschidt and colleagues, they dosed mice with varying concentrations of MK-212, and observed its effects.^[13] 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, head twitches,^[13][8] "an increase in the strength of the crossed extensor reflex in the acutely spinalized rat", and the cause of complex motor syndrome.^[13] In a later study, MK-212 dose-dependently induced the head-twitch response when combined with the selective serotonin 5-HT_2C receptor antagonist SB-242084.^[10] In contrast to the preceding findings, MK-212 has been found to dose-dependently suppress the head-twitch response induced by the serotonergic psychedelic DOI, suggesting that serotonin 5-HT_2C receptor activation may inhibit the head-twitch response.^[14]