Pharmacodynamics +<unk>  Site Ki (nM) Species Ref 1,620–3,300 Human 1,262 Human 6,530 Human 5-HT1A 2,800 Human 5-HT2A 217–280 Human/rat 5-HT2C 206 Rat α1 2,300 Human α2 8,600 Human β >10,000 Mammal D2 6,300 Rat H1 100–130 Human/rat H2 200–8,300 Guinea pig 2,100 Human σ1 >10,000 Rat Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site.<unk>  is unique compared to most other TCAs in that it is a very weak and negligible inhibitor of the reuptake of serotonin and norepinephrine and appears to act instead as a selective albeit weak antagonist of 5-HT2 receptors; hence its classification by some as "second-generation". Additionally,<unk>  has very weak/negligible antiadrenergic and anticholinergic activity and weak although possibly significant antihistamine activity; as such, side effects of<unk>  are much less prominent relative to other TCAs, and it is well tolerated. However,<unk>  may not be as effective as other TCAs, particularly in terms of anxiolysis. Based on animal research, the antidepressant effects of<unk>  may be mediated through downstream dopaminergic mechanisms. The binding affinities of<unk>  for various biological targets are presented in the table to the right. It is presumed to act as an inhibitor or antagonist/inverse agonist of all sites. Considering the range of its therapeutic concentrations (e.g., 63–271 nM at 90 mg/day), only the actions of<unk>  on the 5-HT2 and histamine receptors might be anticipated to be of possible clinical significance. However, it is unknown whether these actions are in fact responsible for the antidepressant effects of<unk> . The plasma protein binding of<unk>  and hence its free percentage and potentially bioactive concentrations do not seem to be known. Pharmacokinetics Only one study appears to have evaluated the pharmacokinetics of<unk> . A single oral dose of 60 mg<unk>  to healthy volunteers has been found to achieve mean peak plasma concentrations of 67.1 ng/mL (236 nmol/L) after 2 to 4 hours. The mean terminal half-life of<unk>  was 52.5 hours, which is notably much longer than that of other TCAs like amitriptyline and imipramine. Following chronic treatment with 90 mg/day<unk>  for 3 weeks, plasma concentrations of the drug ranged between 18 and 77 ng/mL (63–271 nmol/L). Theoretical steady-state concentrations should be reached by 99% within 15 to 20 days of treatment.
Iprindole
Sertindole
Pirlindole
Butriptyline
Selegiline
Bromocriptine
Iobitridol
Rimonabant