Pharmacodynamics +<unk>  Site Ki (nM) Species Ref 4,000 Human 71 Human 9,400 Human 5-HT1A 400–2,600 Human 5-HT1B ≥2,800 Rat 5-HT1D 220–400 Human 5-HT1E 5-HT1F 13 Human 5-HT2A 1.6–55 Human 5-HT2B 1.6–20 Human 5-HT2C 0.63–6.5 Human 5-HT3 5.8–300 Rodent 5-HT4 5-HT5A 5-HT6 55–81 Human 5-HT7 48–56 Human α1 34 Human α2 73 Human α2A 4.8 Human α2B 27 Human α2C 3.8 Human D1 426–1,420 Human D2 2,100–2,700 Human D3 2,840 Human D4 D5 H1 0.30–1.7 Human H2 437 Human H3 95,500 Human H4 >100,000 Human 820 Human 21,000 Human 30,200 Human 530 () Human Values are Ki (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site.<unk>  appears to exert its effects via antagonism of histamine and serotonin receptors, and inhibition of norepinephrine reuptake. More specifically, it is an antagonist/inverse agonist at most or all sites of the histamine H1 receptor, serotonin 5-HT1D, 5-HT1F, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT6, and 5-HT7 receptors, and adrenergic α1- and α2-adrenergic receptors, and additionally a norepinephrine reuptake inhibitor. As an H1 receptor inverse agonist with high affinity,<unk>  has strong antihistamine effects (e.g., sedation). Conversely, it has low affinity for the muscarinic acetylcholine receptors, and hence lacks anticholinergic properties.<unk>  has been found to be a low affinity but potentially significant partial agonist of the κ-opioid receptor (Ki = 1.7 μM; EC50 = 0.53 μM), similarly to some tricyclic antidepressants (TCAs). Blockade of the H1 and possibly α1-adrenergic receptors has sedative effects, and also antagonism of the 5-HT2A and α1-adrenergic receptors inhibits activation of intracellular phospholipase C (PLC), which seems to be a common target for several different classes of antidepressants. By antagonizing the somatodendritic and presynaptic α2-adrenergic receptors which function predominantly as inhibitory autoreceptors and heteroreceptors,<unk>  disinhibits the release of norepinephrine, dopamine, serotonin, and acetylcholine in various areas of the brain and body. Along with mirtazapine, although to a lesser extent in comparison,<unk>  has sometimes been described as a noradrenergic and specific serotonergic antidepressant (NaSSA). However, the actual evidence in support of this label has been regarded as poor. Pharmacokinetics The bioavailability of<unk>  is 20 to 30%. Its plasma protein binding is 95%.<unk>  is metabolized in the liver by the CYP2D6 enzyme via N-oxidation and N-demethylation. Its elimination half-life is 21 to 61 hours. The drug is excreted 4 to 7% in the urine and 14 to 28% in feces.
Mianserin
Ketanserin
Nabilone
Triptan
Seltorexant
Sumatriptan
Naratriptan
Zolmitriptan