Pharmacodynamics +<unk>  (and metabolite) Site Species Ref 1.3–1.4 17.6–163 Human 20–37 0.63–3.5 Human 8,500 3,190 Human 5-HT1A ≥5,800 ≥6,400 Human 5-HT2A 80–150 115–350 Human 5-HT2C 120 244–748 Human/rat 5-HT3 970–3,651 ≥2,500 Rodent 5-HT6 190–209 Rat 5-HT7 >1,000 >1,000 Rat α1 32 23–130 Human α2 3,100 ≥1,379 Human β >10,000 ≥1,700 Rat D1 >10,000 5,460 Human D2 620–726 3,400 Human D3 387 Human H1 7.6–37 60–110 Human H2 550 1,550 Human H3 >100,000 >100,000 Human H4 24,000 9,550 Human 46 66–198 Human M1 42 110 Human M2 88 540 Human M3 60 210 Human M4 112 160 Human M5 83 143 Human α3β4 410–970 Human σ1 332–520 1,990–4,000 Rodent σ2 327–2,100 ≥1,611 Rat 3,400 Human Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site.<unk>  affects numerous neurotransmitter systems known to be involved in the etiology of depression, anxiety, attention-deficit hyperactivity disorder (ADHD), enuresis and numerous other mental and physical conditions.<unk>  is similar in structure to some muscle relaxants, and has a significant analgesic effect and, thus, is very useful in some pain conditions. The mechanisms of<unk> 's actions include, but are not limited to, effects on: * Serotonin: very strong reuptake inhibition. * Norepinephrine: strong reuptake inhibition. Desipramine has more affinity to norepinephrine transporter than<unk> . * Dopamine:<unk>  blocks D2 receptors.<unk> , and its metabolite desipramine, have no appreciable affinity for the dopamine transporter (Ki = 8,500 and >10,000 nM, respectively). * Acetylcholine:<unk>  is an anticholinergic, specifically an antagonist of the muscarinic acetylcholine receptors. Thus, it is prescribed with caution to the elderly and with extreme caution to those with psychosis, as the general brain activity enhancement in combination with the "dementing" effects of anticholinergics increases the potential of<unk>  to cause hallucinations, confusion and delirium in this population. * Epinephrine:<unk>  antagonizes adrenergic receptors, thus sometimes causing orthostatic hypotension. * Sigma receptor: activity on sigma receptors is present, but it is very weak (Ki = 520 nM) and it is about half that of amitriptyline (Ki = 300 nM). * Histamine:<unk>  is an antagonist of the histamine H1 receptors. * BDNF: BDNF is<unk> plicated in neurogenesis in the hippocampus, and studies suggest that depressed patients have decreased levels of BDNF and reduced hippocampal neurogenesis. It is not clear how neurogenesis restores mood, as ablation of hippocampal neurogenesis in murine models do not show anxiety related or depression related behaviours. Chronic<unk>  administration results in increased histone acetylation (which is associated with transcriptional activation and decondensed chromatin) at the hippocampal BDNF promoter, and also reduced expression of hippocampal HDAC5. Pharmacokinetics Within the body,<unk>  is converted into desipramine (desmethylimipramine) as a metabolite.
Imipramine
Desipramine
Clomipramine
Trimipramine
Sertraline
Citalopram
Carpipramine
Methylphenidate