Pharmacodynamics +<unk>  Site Ki (nM) Species Ref 5,800 Human 11–12 Human 1,000 Human 5-HT2A 51 Rat 5-HT2C 122 Rat 5-HT6 5-HT7 50 Guinea pig α1 90 Human α2 9,400 Human D1 402 Human D2 350–665 Human D3 504 Human D4 D5 429 Human H1 0.79–2.0 Human H2 776 Human H3 66,100 Human H4 85,100 Human 570 Human Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site.<unk>  exhibits strong effects as a norepinephrine reuptake inhibitor with only weak actions the reuptake of serotonin and dopamine. It is also a strong antagonist of the H1 receptor, a moderate antagonist of the 5-HT2 and α1-adrenergic receptors, and a weak antagonist of the D2 and muscarinic acetylcholine receptors.<unk>  has also more recently been identified as a potent antagonist of the 5-HT7 receptor, with this action potentially playing an important role in its antidepressant effectiveness. The drug is a strong antihistamine, but unlike most TCAs, has minimal anticholinergic effects. The pharmacological profile of<unk>  explains its antidepressant, sedative, anxiolytic, and sympathomimetic activities. In accordance to the pharmacological characteristics it is used in the treatment of depression, such as depression associated with agitation or anxiety. Additionally, it shows strong antagonism against reserpine-induced effects in animal studies, as do the other 'classical' antidepressants. Although<unk>  behaves in most regards as a 'first-generation antidepressant' it is commonly referred to as 'second-generation antidepressant'. The postulated mechanism of<unk>  is that it acts primarily by potentiation of central adrenergic synapses by blocking reuptake of norepinephrine at nerve endings. This pharmacological action is thought to be primarily responsible for the drug's antidepressant and anxiolytic effects. It is a strong norepinephrine reuptake inhibitor with only weak effects on serotonin and dopamine reuptake. At higher doses however,<unk>  increases serotonergic transmission and increases the level of serotonin available. Pharmacokinetics After oral use absorption is good. It binds to plasma proteins 80–90%. Maximal plasma concentration is reached 6 hours after use. The mean time to peak is 12 hours. The terminal half-life of averages 51 hours.
Maprotiline
Ibutilide
Flecainide
Procainamide
Nortilidine
Dofetilide
Tocainide
Colestilan