Amoxapine GlyT inhibitor

Amoxapine displays a selective inhibition of GLYT2a behaving as a 10 fold more efficient inhibitor of this isoform than of GLYT1b in human embryonic kidney 293 cells. This compound behaves as a competitive inhibitor of both glycine and chloride and a mixed-type inhibitor with respect to sodium. [1] It causes acute hERG blockade in oocytes with IC50 of 21.6 mM and in HEK 293 cells with IC50 of 5.1 mM. This chemical block is reverse frequency-dependent and causes accelerated and leftward-shifted inactivation. Its application results in chronic reduction of hERG trafficking into the cell surface membrane with IC50 of 15.3 mM in HEK 293 cells. [2]

Amoxapine (10 mg/kg i.p., daily) does not affect the levels of dynorphin, substance P and cholecystokinin, but markedly enhances the levels of leu-enkephalin in spinal cord, cerebral cortex and hypothalamus of rats. This compound (10 mg/kg i.p., daily) results in no changes in opioid receptors in the cerebral cortex, but the densities of delta and mu opioid binding sites are increased in the spinal cord, and decreased in the hypothalamus of rats. [3] This chemical (1 mg/kg, 5 mg/kg and 10 mg/kg; i.p.) decreases paradoxical sleep and increases deep slow wave sleep especially when it is given at a low dose. It (10 mg/kg; i.p.) induces a sustained decrease of paradoxical sleep during the whole treatment, while some tolerance is observed with regard to the inhibitory effect of cericlamine on this state of sleep. [4] It decreases locomotor activity, induce ptosis and catalepsy, inhibits apomorphine gnawing and amphetamine stereotyped behavior and by characteristic changes in monkey discriminated avoidance behavior. [5]