Asenapine

Описание

(±)-Asenapine is an atypical antipsychotic. It binds to dopamine D_1-4, α-adrenergic, and histamine receptors (K_is = 0.42-1.45, 0.32-1.26, and 1-6.17 nM, respectively), as well as the serotonin (5-HT) receptor subtypes 5-HT_1A, 5-HT_1B, 5-HT_2A, 5-HT_2B, 5-HT_2C, 5-HT_5A, 5-HT₆, and 5-HT₇ (K_is = 0.03-3.98 nM). (±)-Asenapine inhibits the suppression of neuron firing induced by the 5-HT_2A, dopamine D₂, and α₂-adrenergic receptor agonists 2,5-dimethoxy-4-iodoamphetamine (DOI), apomorphine, and clonidine , respectively, in rat brain (ED₅₀s = 75, 40, and 85 μg/kg, respectively). In vivo, (±)-asenapine (0.05-0.2 mg/kg, s.c.) increases extracellular dopamine levels in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), and lateral striatum and suppresses the conditioned avoidance response in rats. It prevents acute and chronic phencyclidine-induced deficits in cued reversal learning in rats when administered at a dose of 0.075 mg/kg. Formulations containing asenapine have been used in the treatment of schizophrenia and bipolar I disorder.

Химические свойства

Yellow Oil

Использование

Combined serotonin (5HT2) and dopamine (D2) receptor antagonist; structurally related to Mianserin. Antipsychotic

Биологическая активность

Novel psychopharmacologic agent. Displays antagonist activity at 5-HT, dopamine, noradrenalin and histamine receptor subtypes (pK i values are 8.60, 8.40, 10.15, 9.75, 10.46, 8.84, 9.60, 9.94, 8.85, 8.90, 8.84, 9.38, 8.95, 8.93, 8.9, 9.49, 8.91, 9.00 and 8.21 for 5-HT 1A , 5-HT 1B , 5-HT 2A , 5-HT 2B , 5-HT 2C , 5-HT 5A , 5-HT 6 , 5-HT 7 , D 1 , D 2L , D 2S , D 3 , D 4 , α 1A , α 2A , α 2B , α 2C , H 1 and H 2 receptors respectively). Displays no appreciable affinity for muscarinic receptors. Exhibits potent activity in animal models predictive of antipsychotic efficacy.

Ферментативный ингибитор

This atypical antipsychotic agent (FW = 285.77 g/mol; CAS 65576-45-6), marketed under the trade names Saphris ?, and also known as Org 5222 and (3aRS,12bRS)-rel-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenz[2,3: 6,7]-oxepino-[4,5-c]pyrrole, is multi-receptor antagonist with the following spectrum of binding interactions: serotonin 5-HT1A receptor, Ki = 2.5 nM; serotonin 5-HT1B receptor, Ki = 4.0 nM; serotonin 5-HT2A receptor, Ki = 0.06 nM; serotonin 5-HT2B receptor, Ki = 0.16 nM; serotonin 5-HT2C receptor, Ki = 0.03 nM; serotonin 5-HT5A receptor, Ki = 1.6 nM; serotonin 5-HT6 receptor, Ki = 1.5 nM; serotonin 5-HT7 receptor, Ki = 0.13 nM; a1- Adrenergic receptor, Ki = 1.2 nM; a2A-Adrenergic receptor, Ki = 1.2 nM; a2B-Adrenergic receptor, Ki = 0.25 nM; a2C-Adrenergic receptor, Ki = 1.2 nM; dopamine D1-receptor, Ki = 1.4 nM; dopamine D2-receptor, Ki = 1.3 nM; dopamine D3-receptor, Ki = 0.4 nM; dopamine D4-receptor, Ki = 1.1 nM; histamine H1-receptor, Ki = 1.0 nM; and histamine H2-receptor, Ki = 6 nM. Like other atypical antipsychotic drugs, asenapine preferentially enhances dopamine and acetylcholine efflux in the rat medial prefrontal cortex and hippocampus. See Reference-x for asenapine’s UV, IR, NMR, and mass spectra as well as X-ray analysis, thermal properties, solubilities and partition coefficient.