N,N-ジメチル-3-[(Z)-ジベンゾ[b,e]オキセピン-11(6H)-イリデン]-1-プロパンアミン

Obtain an ECG and immediately initiate cardiac monitoring. Protect the patient's airway, establish an intravenous line and initiate gastric decontamination. A minimum of six hours of observation with cardiac monitoring and observation for signs of CNS or respiratory depression, hypotension, cardiac dysrhythmias and/or conduction blocks, and seizures is strongly advised. If signs of toxicity occur at any time during this period, extended monitoring is recommended. (L1712)

hypotension, postural collapse (if patient arises too fast from lying/sitting position to standing), arrhythmias (sinus-tachycardia, bradycardia, av-blockade). Allergic/toxic effetcs also include skin rash, photosensitivity, liver damage of the cholostatic type (rarely), hepatitis (extremely rare), leuko- or thrombopenia (rarely), agranulocytosis (very rarely), hypoplastic anemia (rarely). [Wikipedia]

The mechanism of action of doxepin is not completely understood. It is thought that like amitriptyline, doxepin enhances the actions of norepinephrine and serotonin by blocking their reuptake at the neuronal membrane. However, doxepin weakly inhibits the reuptake of dopamine. Doxepin may also act on histamine H₁-receptors, resulting in sedative effects, and β-adrenergic receptors. It is also an antagonist of 5-hydroxytryptamine (serotonin) receptors, alpha-1 adrenergic receptor, and muscarinic cholinergic receptors.

Similar to other tricyclic antidepressants, doxepin was shown, in preclinical trials, to decrease the electrical activity of the brain, prolong the hexobarbital-induced sleep and block avoidance behavior without affecting the conditioned emotional response. At high doses, it also produces symptoms of central nervous system depression. Doxepin is known to cause antidepressant, sedative, and anticholinergic effects. At high doses, its anticholinergic and antiadrenergic properties are the most prevalent which limit its efficacy. These effects are observed at high doses where its affinity for H1 histamine receptor is lost and its binding to other receptors is observed. The maximal antidepressive effects of doxepin are present around two weeks following initiation of therapy. However, the sedative effects of doxepin, usually used for the treatment of insomnia or anxiety, are observed immediately after administration.

Doxepin exact mechanism of action is not very clear. However, doxepin is known to be a selective histamine H1 receptor blocker. This effect on histamine receptors indicates effectiveness in skin conditions. Breaking its function according to the different effect, doxepin's antidepressive action is primarily associated with the inhibition of the central nervous system biogenic amine reuptake; more specifically, norepinephrine and serotonin at synaptic nerve terminals. This effect increases the level of monoamines in the synaptic site which in order increases the activity at the post-synaptic neuron receptor sites. It has been suggested that doxepin also desensitizes both serotonin 1A receptors and beta-adrenergic receptors. It is known that the lack of dopamine transporters in the frontal cortex and the transmission of dopamine in this region is largely inactivated by the effect of norepinephrine reuptake. Hence, doxepin action on the frontal cortex is suggested to increase dopamine neurotransmission in this area.