Pharmacodynamics +<unk>  Site Ki (nM) Species Ref 200–459 Human 360–618 Human 360 Human 5-HT1A 80 Human 5-HT2A 26 Human 5-HT2C 72 Human α1 5.5–48 Human α1A 48 Human α2 84–640 Human β >10,000 Rat D2 910 Human H1 ≥370 Human >10,000 Human Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site.<unk>  acts primarily as a potent antagonist of the serotonin 5-HT2A receptor and to a lesser extent of the serotonin 5-HT2C receptor. It also has high affinity for the α1-adrenergic receptor and serotonin 5-HT1A receptor, and relatively lower affinity for the α2-adrenergic receptor and dopamine D2 receptor.<unk>  has low but significant affinity for the serotonin, norepinephrine, and dopamine transporters as well, and therefore acts as a weak serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI). It has low but potentially significant affinity for the histamine H1 receptor, where it is an antagonist, and hence may have some antihistamine activity.<unk>  has negligible activity at muscarinic acetylcholine receptors, and accordingly, has no anticholinergic effects. Pharmacokinetics The bioavailability of<unk>  is low and variable, about 20%. Its plasma protein binding is approximately 99%, but it is bound loosely.<unk>  is metabolized in the liver, with the main enzyme involved thought to be CYP3A4. The drug has at least four active metabolites, which include hydroxynefazodone, para-hydroxynefazodone, triazoledione, and meta-chlorophenylpiperazine.<unk>  has a short elimination half-life of about 2 to 4 hours. Its metabolite hydroxynefazodone similarly has an elimination half-life of about 1.5 to 4 hours, whereas the elimination half-lives of triazoledione and mCPP are longer at around 18 hours and 4 to 8 hours, respectively. Due to its long elimination half-life, triazole is the major metabolite and predominates in the circulation during<unk>  treatment, with plasma levels that are 4 to 10 times higher than those of<unk>  itself. Conversely, hydroxynefazodone levels are about 40% of those of<unk>  at steady state. Plasma levels of mCPP are very low at about 7% of those of<unk> ; hence, mCPP is only a minor metabolite. mCPP is thought to be formed from<unk>  specifically by CYP2D6. The ratios of brain-to-plasma concentrations of mCPP to<unk>  are 47:1 in mice and 10:1 in rats, suggesting that brain exposure to mCPP may be much higher than plasma exposure. Conversely, hydroxynefazodone levels in the brain are 10% of those in plasma in rats. As such, in spite of its relatively low plasma concentrations, brain exposure to mCPP may be substantial, whereas that of hydroxynefazodone may be minimal.
Nefazodone
Hydrocodone
Vilazodone
Tapentadol
Tramadol
Noroxycodone
Morphine
Methadone