F17464 / Pierre Fabre - LARVOL DELTA

Unlocking the potential of lumateperone and novel anti-psychotics for schizophrenia. (PubMed, Bioimpacts) - "This review also focuses on a few more emerging antipsychotics like brexpiprazole, brilaroxazine, roluperidone, F17464, pimavanserin (ACP-103), xanomeline, BI 409306, BI 425809 and MK-8189 which are under different phase of clinical trials and might get approved soon. All the antipsychotic drugs covered did not show any other severe adverse effects except gastrointestinal issues and cardiometabolic risk factors. However, still rigorous clinical trials and modifications are needed to manage adverse effects, and we can expect a few antipsychotics to be on the market soon."

Journal • Review • Anesthesia • CNS Disorders • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • Psychiatry • Schizophrenia

New and emerging treatments for schizophrenia: a narrative review of their pharmacology, efficacy and side effect profile relative to established antipsychotics. (PubMed, Neurosci Biobehav Rev) - "Cariprazine, brexpiprazole and brilaroxazine are partial dopamine agonists effective in acute relapse. Lumateperone (serotonin and dopamine receptor antagonist) additionally benefits asocial and depressive symptoms. F17464 (D3 antagonist and 5-HT1A partial agonist) has one positive phase II study. Lu AF35700 (dopamine and serotonin receptor antagonist) was tested in treatment-resistance with no positive results. Pimavanserin, roluperidone, ulotaront and xanomeline do not act directly on the D2 receptor at clinical doses...BI 409306, BI 425809 and MK-8189 target glutamatergic dysfunction in schizophrenia, though of these only BI 425809 showed efficacy. These medications largely have favourable cardiometabolic side-effect profiles. Overall, the novel pharmacology, clinical trial and tolerability data indicate these compounds are promising new additions to the therapeutic arsenal."

Adverse events • Clinical • Journal • Review • CNS Disorders • Psychiatry • Schizophrenia

Pharmacology profile of F17464, a dopamine D receptor preferential antagonist. (PubMed, Eur J Pharmacol) - "In human dopaminergic neurons F17464 blocks ketamine induced morphological changes, an effect D3 receptor mediated...F17464 increases dopamine release in the rat prefrontal cortex and mouse lateral forebrain - dorsal striatum and seems to reduce the effect of MK801 on % c-fos mRNA medium expressing neurons in cortical and subcortical regions...All the neurochemistry and behavioural effects of F17464 are observed in the dose range 0.32-2.5 mg/kg i. p in both rats and mice. The in vitro - in vivo pharmacology profile of F17464 in preclinical models is discussed in support of a therapeutic use of the compound in schizophrenia and autism."

Journal • Autism Spectrum Disorder • CNS Disorders • Genetic Disorders • Psychiatry • Schizophrenia

Keeping up with the therapeutic advances in schizophrenia: a review of novel and emerging pharmacological entities. (PubMed, CNS Spectr) - "Therapies targeting total symptoms include cannabidiol, D3 antagonist/5-HT1A partial agonist F17464, lumateperone (ITI-007), phosphodiesterase 10A (PDE10A) inhibitors MK-8189 and TAK-063, sodium nitroprusside, and trace amine-associated receptor-1 (TAAR1) agonist RO5263397 and SEP-363856. Treatments targeting negative symptoms include the PDE10A inhibitor LuAF-11167, 5-HT2A inverse agonist pimavanserin, sigma-2/5-HT2A antagonist roluperidone (MIN-101), and d-amino acid oxidase (DAAO) inhibitor TAK-831. Agents targeting primarily cognitive dysfunction are the glycine transporter-1 inhibitor BI-425809 and cannabidiol. Therapies targeting residual positive symptoms/treatment-resistant schizophrenia include pimavanserin, dopamine D1/D2 antagonist LuAF-35700, and DAAO inhibitor sodium benzoate. Two new long-acting injectable antipsychotic formulations, Aripiprazole Lauroxil NanoCrystal® and the first subcutaneous injectable LAI Perseris (RBP-7000), were recently approved..."

Journal • CNS Disorders • Schizophrenia

Binding of the D3-preferring antipsychotic candidate F17464 to dopamine D3 and D2 receptors: a PET study in healthy subjects with [C]-(+)-PHNO. (PubMed, Psychopharmacology (Berl)) - "Overall, F17464 was strongly D3-selective in healthy volunteers, a unique profile for an antipsychotic candidate drug."

Clinical • Journal • CNS Disorders • Schizophrenia

Randomized, double-blind, placebo-controlled study of F17464, a preferential D antagonist, in the treatment of acute exacerbation of schizophrenia. (PubMed, Neuropsychopharmacology) - "Interestingly, no weight gain, no extrapyramidal disorder except rare akathisia were observed under F17464. This 6-week trial demonstrated therapeutic efficacy of 40 mg/day F17464 in improving symptoms of acute exacerbation of schizophrenia with a favorable safety profile."

Clinical • Journal • CNS Disorders • Schizophrenia

Pharmacological Treatment of Negative Symptoms: New Findings and Perspectives (EPA 2019) - "...Two dopamine D3-receptor-preferring partial agonists, F17464 (it is in Phase II) and cariprazine (it is already on the market) showed efficacy against positive symptoms, cariprazine has been found also effective against predominant and persistent negative symptoms as compared to risperidone...An example is pimavanserin, which is an inverse agonist and antagonist at serotonin 5-HT2A receptors with high binding affinity and at serotonin 5-HT2C receptors with lower binding affinity...This drug has already been approved by the FDA for the treatment of hallucinations and delusions associated with Parkinsons disease psychosis. An interesting further approach is to discontinue antipsychotic drugs in stable schizophrenia patients with negative symptoms and start a drug for the treatment of negative symptoms, such as MIN-101, a 5HT2 and Sigma 2 antagonist, which demonstrated statistically significant efficacy as a monotherapy; and Lu AF11167 (an inhibitor of a..."