SEP-363856 does not bind to dopamine 2 (D2) or serotonin 2A (5-HT2A) receptors, which are thought to mediate the effects of currently available atypical antipsychotic medicines. Instead, SEP-363856 activates TAAR1 (trace amine-associated receptor 1) and 5-HT1A (serotonin 1A) receptors.
That is pretty interesting. Even though it does not directly bind dopamine it apparently modulates presynaptic dopamine.
“The Novel, Non-D2 Psychotropic Agent SEP-363856 Modulates Presynaptic Dopamine Function in Mice,”
We synthesize this evidence into a new dopamine hypothesis of schizophrenia-version III: the final common pathway. This hypothesis seeks to be comprehensive in providing a framework that links risk factors, including pregnancy and obstetric complications, stress and trauma, drug use, and genes, to increased presynaptic striatal dopaminergic function. It explains how a complex array of pathological, positron emission tomography, magnetic resonance imaging, and other findings, such as frontotemporal structural and functional abnormalities and cognitive impairments, may converge neurochemically to cause psychosis through aberrant salience and lead to a diagnosis of schizophrenia.
Adverse events occurring in at least five percent of patients included exacerbation of schizophrenia (12.2 percent), headache (11.5 percent), insomnia (8.3 percent), and anxiety (5.1 percent). Additionally, effects on weight, lipids, glycemic indices, prolactin and extrapyramidal symptoms (EPS) measures were negligible and not clinically meaningful. The proportion of patients who experienced EPS during the 26 weeks of treatment with SEP-363856 was 3.2 percent.
he study also showed that patients treated with SEP-363856 demonstrated clinically meaningful improvements across all efficacy measures, including the Positive and Negative Syndrome Scale (PANSS) total score (-22.6), the Clinical Global Impression Scale - Severity (CGI-S) score (-1.0), and the Brief Negative Symptom Scale (BNSS) total score (-11.3).
Is it just me or is that pretty good for negative symptoms as well?
The study had a completion rate of 66.9 percent, and the discontinuation rate due to an adverse event was 11.5 percent. Adverse events occurring in at least five percent of patients included exacerbation of schizophrenia (12.2 percent), headache (11.5 percent), insomnia (8.3 percent), and anxiety (5.1 percent).