Second Generation Antidepressants: A Comparative Review

Abstract

The authors review four "second generation" antidepressants (maprotiline, amoxapine, trazodone, and nomifensine) in terms of action on biogenic amines and receptors, antidepressive efficacy, and adverse effects. Doxepin is used as a comparative agent and is similar to the prototypical tricyclic agents in all the above categories. Maprotiline is a selective noradrenergic agent, but shares a similar adverse effect profile with doxepin and may be associated with a high frequency of seizures in overdose. Amoxapine is a mixed action antidepressant with significant neuroleptic activity in vivo. Its adverse effect profile is highlighted by symptoms related to its neuroleptic activity, and seizures and acute renal failure in overdose. Trazodone is a selective serotonergic agent with low anticholinergic activity, and minimal morbidity/mortality in overdose. Reports of priapism, leading to impotence in some men, however, is of concern. Nomifensine is a potent noradrenergic and dopaminergic agent with low anticholinergic activity, and minimum cardiotoxicity and low morbidity/mortality in overdose. Its most important adverse effects include overstimulation and infrequent, usually reversible, immunologic hypersensitivity reactions. Trazodone and nomifensine have favorable profiles for use in the elderly. Trazodone may be more favorable in the anxious/agitated patient due to its sedative effects, whereas nomifensine may be more beneficial in the retarded, apathetic patient.

Reinvestigation of alternative method for the preparation of dibenz[b,f][1,4]oxazepine

“…The pathway A afforded more convenient and soft conditions for the production of pure 7 and its intermediates. Fluoro derivative of 1 afforded excellent, more convenient and soft conditions for the one-pot preparation of target compound (7). The presence of only trans configuration for the imine 6 (produced from 3 with 4) and the impossibility of its conversion to cis, makes it inadequate for the preparation of 7.…”

“…Dibenz[b,f] [1,4]oxazepine (7,CR) is an incapacitating lachrymatory agent [1][2][3][4][5][6] and is an intermediate in the synthesis of loxapine (antipsychotic), amoxapine (antidepressant) [7], and others substituted dibenzoxazepine compounds that are analgesic or useful for the treatment of different diseases [8][9][10][11].…”

Monitoring of the Effects of Antidepressant Drugs in the Freely Moving Rat by Radioelectroencephalography (Tele-Stereo-EEG)

“…In terms of biochemical char acterization there is no common feature linking them together as for example nomifensine is predominantly regarded as a catecholamine reuptake inhibitor [Koe, 1976]; amitriptyline has been related to noradrenergic transmission, while imipramine has been described as a noradrenergic and serotonergic uptake inhibitor [Sulser and Mobley, 1980], Catecholamine/indolamine uptake has likewise but to a lesser degree been ascribed to the action of doxepine [for a review of biochemical charac teristics of antidepressants see Coccaro and Siever, 1985], Our results on the one hand reflect a diversity of action, but on the other hand common effects can be recognized in terms of the pattern of changes which is more or less pronounced under the different drug condi tions. All antidepressant drugs influence virtually all fre quency bands in all brain areas.…”

Amoxapine as an Atypical Antipsychotic: A Comparative Study Vs Risperidone

“…There were no reports of overdosing in the present study. The ingestion of doses superior to 1500 mg of amoxapine has been associated to multiple seizures, severe metabolic acidosis, acute renal failure, and coma (Coccaro and Siever, 1985). However, reports of death with amoxapine overdosage are only about 4% (Bishop and Kiltie, 1983).…”