<unk>  is classified as a low-potency typical antipsychotic. Low-potency antipsychotics have more anticholinergic side effects, such as dry mouth, sedation, and constipation, and lower rates of extrapyramidal side effects, while high-potency antipsychotics (such as haloperidol) have the reverse profile. Pharmacokinetics + Pharmacokinetic parameters of<unk>  Bioavailability tmax CSS Protein bound Vd t1/2 Details of metabolism Excretion Notes 10–80% 1–4 hours (Oral); 6–24 hours (IM) 100–300 ng/mL 90–99% 10–35 L/kg (mean: 22 L/kg) 30±7 hours CYP2D6, CYP1A2—mediated into over 10 major metabolites. The major routes of metabolism include hydroxylation, N-oxidation, sulfoxidation, demethylation, deamination and conjugation. There is little evidence supporting the development of metabolic tolerance or an increase in the metabolism of<unk>  due to microsomal liver enzymes following multiple doses of the drug. Urine (43–65% after 24 hours) Its high degree of lipophilicity (fat solubility) allows it to be detected in the urine for up to 18 months. Less than 1% of the unchanged drug is excreted via the kidneys in the urine, in which 20–70% is excreted as conjugated or unconjugated metabolites, whereas 5–6% is excreted in feces. Three common metabolites of<unk>  Pharmacodynamics<unk>  Site Ki Species Ref 5-HT1A 3115 Human 5-HT1B 1,489 Human 5-HT1D 452 Human 5-HT1E 344 Human 5-HT2A 2.75 Human 5-HT2C 25 Human 5-HT3 776 Human 5-HT5A 118 Human 5-HT6 19.5 Human 5-HT7 21 Human α1A 0.28 Human α1B 0.81 Human α2A 184 Human α2B 28 Human α2C 46 Human β1 >10,000 Human β2 >10,000 Human M1 47 Human M2 433 Human M3 47 Human M4 151 Human D1 114.8 Human D2 7.244 Human D3 6.9 Human D4 32.36 Human H1 4.25 Human H2 174 Human H3 1,000 Human H4 5,048 Human NET 2,443 Human DAT >10,000 Human<unk>  is a very effective antagonist of D2 dopamine receptors and similar receptors, such as D3 and D5. Unlike most other drugs of this genre, it also has a high affinity for D1 receptors. Blocking these receptors causes diminished neurotransmitter binding in the forebrain, resulting in many different effects. Dopamine, unable to bind with a receptor, causes a feedback loop that causes dopaminergic neurons to release more dopamine. Therefore, upon first taking the drug, patients will experience an increase in dopaminergic neural activity. Eventually, dopamine production of the neurons will drop substantially and dopamine will be removed from the synaptic cleft. At this point, neural activity decreases greatly; the continual blockade of receptors only compounds this effect.<unk>  acts as an antagonist (blocking agent) on different postsynaptic and presynaptic receptors: *Dopamine receptors (subtypes D1, D2, D3 and D4), which account for its different antipsychotic properties on productive and unproductive symptoms, in the mesolimbic dopamine system accounts for the antipsychotic effect whereas the blockade in the nigrostriatal system produces the extrapyramidal effects *Serotonin receptors (5-HT2, 5-HT6 and 5-HT7), with anxiolytic, antidepressant and antiaggressive properties as well as an attenuation of extrapyramidal side effects, but also leading to weight gain and ejaculation difficulties. *Histamine receptors (H1 receptors, accounting for sedation, antiemetic effect, vertigo, and weight gain) *α1- and α2-adrenergic receptors (accounting for sympatholytic properties, lowering of blood pressure, reflex tachycardia, vertigo, sedation, hypersalivation and incontinence as well as sexual dysfunction, but may also attenuate pseudoparkinsonism – controversial. Also associated with weight gain as a result of blockage of the adrenergic alpha 1 receptor) *M1 and M2 muscarinic acetylcholine receptors (causing anticholinergic symptoms such as dry mouth, blurred vision, constipation, difficulty or inability to urinate, sinus tachycardia, electrocardiographic changes and loss of memory, but the anticholinergic action may attenuate extrapyramidal side effects). The presumed effectiveness of the antipsychotic drugs relied on their ability to block dopamine receptors. This assumption arose from the dopamine hypothesis that maintains that both schizophrenia and bipolar disorder are a result of excessive dopamine activity. Furthermore, psychomotor stimulants like cocaine that increase dopamine levels can cause psychotic symptoms if taken in excess.<unk>  and other typical antipsychotics are primarily blockers of D2 receptors. In fact an almost perfect correlation exists between the therapeutic dose of a typical antipsychotic and the drug's affinity for the D2 receptor. Therefore, a larger dose is required if the drug's affinity for the D2 receptor is relatively weak. A correlation exists between average clinical potency and affinity of the antipsychotics for dopamine receptors.<unk>  tends to have greater effect at serotonin receptors than at D2 receptors, which is notably the opposite effect of the other typical antipsychotics. Therefore,<unk>  with respect to its effects on dopamine and serotonin receptors is more similar to the atypical antipsychotics than to the typical antipsychotics.<unk>  and other antipsychotics with sedative properties such as promazine and thioridazine are among the most potent agents at α-adrenergic receptors. Furthermore, they are also among the most potent antipsychotics at histamine H1 receptors. This finding is in agreement with the pharmaceutical development of<unk>  and other antipsychotics as anti-histamine agents. Furthermore, the brain has a higher density of histamine H1 receptors than any body organ examined which may account for why<unk>  and other phenothiazine antipsychotics are as potent at these sites as the most potent classical antihistamines. In addition to influencing the neurotransmitters dopamine, serotonin, epinephrine, norepinephrine, and acetylcholine it has been reported that antipsychotic drugs could achieve glutamatergic effects. This mechanism involves direct effects on antipsychotic drugs on glutamate receptors. By using the technique of functional neurochemical assay<unk>  and phenothiazine derivatives have been shown to have inhibitory effects on NMDA receptors that appeared to be mediated by action at the Zn site. It was found that there is an increase of NMDA activity at low concentrations and suppression at high concentrations of the drug. No significant difference in glutamate and glycine activity from the effects of<unk>  were reported. Further work will be necessary to determine if the influence in NMDA receptors by antipsychotic drugs contributes to their effectiveness.<unk>  does also act as a FIASMA (functional inhibitor of acid sphingomyelinase). Peripheral effects<unk>  is an antagonist to H1 receptors (provoking antiallergic effects), H2 receptors (reduction of forming of gastric juice), M1 and M2 receptors (dry mouth, reduction in forming of gastric juice) and some 5-HT receptors (different anti-allergic/gastrointestinal actions). Because it acts on so many receptors,<unk>  is often referred to as a "dirty drug".
Chlorpromazine
Chlortalidone
Clozapine
Desmethylclozapine
Haloperidol
Thioridazine
Trimipramine
Primidone