TriRima™ is currently in Phase II clinical trials following a successful Phase I program. A recently completed brain PET imaging study demonstrated TriRima’s ability to potently block the MAO-A enzyme, confirming its mechanism of action. The PET imaging study confirmed that TriRima is both a potent and reversible MAO-A inhibitor in humans. The study confirmed TriRima as a potent, but reversible MAO-A inhibitor. The safety and tolerability of TriRima have been confirmed in over 100 human subjects. The data in this section includes highlights from a number of studies that have demonstrated TriRima’s ability to:
The image on the left (A) in figure 1 depicts a human brain PET scan showing high levels of MAO-A binding by a radiolabeled MAO-A specific ligand – this scan is taken prior to the administration of TriRima. The image on the right (B) was taken 2 hours following a 60mg dose of TriRima and shows a significant reduction in MAO-A binding. By blocking the binding and activity of MAO-A, TriRima serves to elevate the key neurotransmitters associated with relieving depression (serotonin, norepinephrine and dopamine).
In preclinical studies, TriRima demonstrated its ability to elevate key neurotransmitters associated with depression as shown in figure 2. Its preferential effect on serotonin, followed by its subsequent effects on norepinephrine and then dopamine, is believed to optimize efficacy and minimize the cardiovascular side effects and abuse potential that have challenged the successful development of triple-reuptake inhibitors.
TriRima is 100X More Potent vs. Established MAO Inhibitor Moclobemide. In preclinical studies, TriRima was 100 times more potent than the leading MAO inhibitor moclobemide. TriRima also demonstrated greater affinity for MAO-A in the CNS than in the liver, further reducing the potential for food effects and the potential need for dietary restrictions. See figure 3.
In preclinical studies, TriRima was highly selective, or specific, for MAO-A versus MAO-B in the CNS. As shown in figure 4, TriRima achieved complete inhibition of MAO-A while having no effect on MAO-B. TriRima’s high level of MAO-A specificity means that MAO-B is still available to metabolize tyramine and prevent the dangerous accumulation that can lead to hypertensive crisis, with the resulting need for dietary restrictions.
As illustrated in Figure 5, state-of-the-art PET/brain imaging studies have shown TriRima to potently block the MAO-A enzyme (B) but unlike older MAO-A inhibitors, TriRima shows reversibility within a 12 hour period (C). Should high levels of tyramine build up, TriRima’s reversibility allows tyramine to “knock” the drug off the MAO-A enzyme, thereby making it possible for the MAO-A enzyme to metabolize the excess tyramine, preventing its dangerous accumulation and the potential for hypertensive crisis.