Antidepressants physicochemical properties

Effect of Physicochemical Properties and Stereochemistry on Antidepressant Efficacy... 

Mirtazapine is a piperazinodibenzoazepine antidepressant that is an isostere of the antidepressant mianserin (Fig. 21.22). A seemingly simple isosteric replacement of an aromatic methine group (CH) in mianserin with a nitrogen to give a pyridine ring (mirtazapine) has profound effects on the physicochemical properties, pharmacokinetics, mechanisms of action, and antidepressant activities (Table 21.12) (31). Profound differenoes between receptor affinity and transporter affinity, pharmacokinetics, regioselectivity in the... 

The lactam (448) was converted to the imidochloride (449) which was treated with piperazine to give amoxapine (450) Scheme 5.106.) [599], Alternatively, the amino ether (451) was acetylated with ethyl chloroform and the product treated with 1-ethoxycarbonylpiperazine to give the urea (452) which underwent the Bischler-Napieralski cyclization to give (450) Scheme 5.106.) [600]. Amoxapine is an antidepressant with rapid onset of action, valuable in the treatment of psychotic depression [601-607]. The chemistry and physicochemical properties of the drug have been reviewed [608,609]. 

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