DMAI

Pharmacodynamics

DMAI shows weak affinity for the serotonin 5-HT_2A receptor (K_i = 1,970 nM). The drug shows no agonism of the serotonin 5-HT_2A receptor, instead acting as a weak antagonist of this receptor. It is a partial agonist of the serotonin 5-HT_2B receptor, with an EC₅₀Tooltip half-maximal effective concentration of 1,630 nM and an E_maxTooltip maximal efficacy of 44%. In addition, it is a potent high-efficacy partial agonist of the serotonin 5-HT_2C receptor, with an EC₅₀ of 334 nM and an E_max of 83%. DMAI is also a high-efficacy agonist of the serotonin 5-HT₁ receptors, with EC₅₀ values of approximately 500 to 800 nM (except 134 nM at 5-HT_1D) and E_max values of greater than 80%. It is a potent and moderate-efficacy partial agonist of the dopamine D₂ receptor, with an EC₅₀ of 588 nM and an E_max of 43%.

In accordance with its lack of serotonin 5-HT_2A receptor agonism, DMAI failed to produce the head-twitch response, a behavioral proxy of psychedelic effects, in rodents. Instead, it suppressed the 5-MeO-DMT-induced head-twitch response and antagonized amphetamine-induced hyperlocomotion, effects suggestive of antipsychotic-like activity. The drug has also been reported to produce sympathomimetic effects in cats, which might be mediated by α₁-adrenergic receptor stimulation or α₂-adrenergic receptor antagonism. It robustly suppresses prolactin levels in rodents, which is assumed to be due to its dopamine D₂ receptor agonism.