Antagonists tetracyclic antidepressants

Mirtazapine is a tetracyclic antidepressant, similar to mianserin, and is a potent 5-HT2a/2c receptor antagonist. It has been successfully used to treat akathisia. In a doubleblind, placebo-controlled study in 26 patients with schizophrenia who were receiving neuroleptic drugs, mirtazapine 15 mg/day for 5 days was associated with less akathisia (227). 

Amoxapine may be the preferred trycyclic/tetracyclic antidepressant to combine with an MAOl in heroic cases due to its theoretically protective 5HT2A antagonist properties... 

Indeed, on the basis of the cyclase assay, amitriptyline is one of the most potent H2-antagonists presently available (KD 0.05 /iM) [ 181, 193]. The dissociation constants for many of the antidepressants are sufficiently low to suggest that the activation of adenylate cyclase by histamine may be inhibited by therapeutically effective concentrations of these compounds [81, 193]. This biochemical action of the tricyclic and tetracyclic antidepressants may thus represent part of the molecular basis of clinical antidepressant activity [193]. It should also be noted that most tricyclic and tetracyclic antidepressants are much more potent inhibitors of H,-receptor responses [67, 120] than they are of the H2-cyclase response, and this property of these compounds may mediate the sedative actions of these drugs [71, 73, 75]. 

Mianserin and maprotiline are tetracyclic antidepressants, which have actions similar to those of the tricyclie antidepressants. However, while the tetracyclics are more sedating, their antimusearinic effects are less marked. Maprotiline inhibits the leuptake of noradrenaline (norepinephrine) and has weak affinity for eentral adrenergic (aj) receptors. Mianserin does not prevent the peripheral reuptake of noradrenaline it blocks presynaptic adrenergic (a2) receptors and increases the turnover of hrain noradrenaline. It is also an antagonist of serotonin receptors in some parts of the brain. 

Mlrtazapine. The tetracyclic mirtazapine (Remenin) is another example of an or-antagonist that shows selectivity for 02 receptors versus serotonin receptors and at histamine H receptors. 

Category Antidepressant, tetracyclic Muscarinic antagonist Half-life I 1-30 hours... 

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