# GM-2505

GM-2505 is a serotonergic psychedelic which is under development for the treatment of major depressive disorder. Its route of administration is intravenous administration.
The drug acts as a potent and well-balanced serotonin 5-HT$_{2A}$ and 5-HT$_{2C}$ receptor agonist, serotonin 5-HT$_{2B}$ receptor antagonist, and serotonin releasing agent. It produces psychedelic-like effects in animals and robust hallucinogenic effects in humans. The drug's duration is 60 to 90 minutes and is intermediate between the durations of dimethyltryptamine (DMT) and psilocybin. The chemical structure of GM-2505 does not appear to have been disclosed, but it is said to be based on and an improvement of DMT.
GM-2505 under development by Gilgamesh Pharmaceuticals. As of March 2024, GM-2505 is in phase 2 clinical trials for the treatment of major depressive disorder.

## Effects

GM-2505 produces effects in humans including "altered states of consciousness, altered visual depth perception, abnormal thinking, euphoric mood, feeling drunk, feeling of body temperature changes, relaxation, sensory processing disorder (including intense visual effects with color changes), sensory overload, and time perception altered". It also produces transient increases in blood pressure. The subjective effects of GM-2505 were described as very robust and consistent in strength with the effects of other serotonergic psychedelics including LSD, dimethyltryptamine (DMT), and psilocybin.

## Pharmacology
### Pharmacodynamics

GM-2505 acts as a potent and well-balanced serotonin 5-HT$_{2A}$ and 5-HT$_{2C}$ receptor agonist, serotonin 5-HT$_{2B}$ receptor antagonist, and serotonin releasing agent.
The affinity (K$_i$) of GM-2505 for the serotonin 5-HT$_{2A}$ receptor was 4.9 nM with DOI as the radioligand and 140 nM with ketanserin as the radioligand. Its EC$_{50}$Tooltip half-maximal effective concentration (E$_{max}$Tooltip maximal efficacy) values were 15.0 nM (80.6%) at the serotonin 5-HT$_{2A}$ receptor and 9.5 nM at the serotonin 5-HT$_{2C}$ receptor, whereas its IC$_{50}$ at the serotonin 5-HT$_{2B}$ receptor was 5.8 nM. GM-2505 showed very weak activity at the serotonin 5-HT$_{1A}$ receptor (EC$_{50}$ = 16,918 nM). In addition to its actions at the serotonin 5-HT$_2$ receptors, partial serotonin releasing agent in rat brain synaptosomes, with an EC$_{50}$ of 15.7 nM and an E$_{max}$ of 66.8%.
GM-2505 is said to be based on DMT and to be a new and improved version of DMT. It also induces more serotonin release than DMT, which may provide it with more entactogen-like qualities. GM-2505 produces the head-twitch response, a behavioral proxy of psychedelic effects, in rodents. It shows antidepressant-like effects in rodents as well.

### Pharmacokinetics

The elimination half-life of GM-2505 in humans is about 45 minutes. Compared to other 5-HT$_{2A}$ receptor agonists like psilocybin, GM-2505 is said to have a shorter duration of action, but is longer-lasting than dimethyltryptamine (DMT). Its duration is about 60 to 90 minutes, whereas psilocybin has a duration of multiple hours and DMT has a duration of as short as 10 minutes.

## Chemistry

The exact chemical structure of GM-2505 does not yet seem to have been disclosed. However, GM-2505 is said to be based on dimethyltryptamine (DMT) and to be structurally related to DMT and psilocybin. In addition, disclosed compounds with the same mechanism of action were patented by Gilgamesh in 2022.

## Clinical development

GM-2505 under development by Gilgamesh Pharmaceuticals. As of March 2024, GM-2505 is in phase 2 clinical trials for the treatment of major depressive disorder.