Abstract
Depression is a severe mental disorder characterized by a major imbalance between the levels of neurotransmitters. US11534436 B2 discloses an efficient amount of μ-opioid receptor agonists or their pharmaceutically acceptable salt for efficient treatment of depression. The patent discloses a few new compounds among which compounds 1, 2, 3, 4, and 5 as well as derivatives of basic nucleus A have good μ-opioid receptor agonist activity without risks of opioid addiction or development of addiction withdrawal symptoms. The compounds displayed Emax of 5% to 45% in a GTPγS binding assay while one of the derivatives displayed Emax of 15% to 35% in a GTPγS binding assay. The patent further discloses different embodiments with different potentials. The administration of an effective dose in rats resulted in 125% to 300% efflux of dopamine of baseline. At a dosage of 1-10 mg/kg, the embodiments do not diminish the thermal pain in rodents. Although the patent explored new μ-opioid receptor agonists for the treatment of depressive symptoms, the exhaustive evaluation of toxicity and further mechanisms need to be explored via in vivo models.
[http://dx.doi.org/10.1007/s11064-022-03755-1] [PMID: 36308619]
[http://dx.doi.org/10.1007/s11064-023-03873-4] [PMID: 36795184]
[http://dx.doi.org/10.1038/s41380-022-01819-w] [PMID: 36253441]
[http://dx.doi.org/10.3109/07420528.2010.516380] [PMID: 20969525]
[http://dx.doi.org/10.1080/14737167.2023.2167712] [PMID: 36697398]
[http://dx.doi.org/10.13172/2053-0285-1-2-978]
[http://dx.doi.org/10.1176/appi.ajp.2009.08081167] [PMID: 20194481]
[http://dx.doi.org/10.1016/0166-2236(95)93946-U] [PMID: 7535487]
[http://dx.doi.org/10.1016/0006-8993(90)91301-V] [PMID: 2176118]
[http://dx.doi.org/10.1124/pharmrev.122.000618] [PMID: 36757901]