Amiabel Mechanism of Action





United Lab
Full Prescribing Info
Pharmacology: Amisulpride is a substituted benzamide atypical antipsychotic. It binds selectively with a high affinity to human dopaminergic D2 and D3 receptor subtypes while having no affinity for D1, D4 and D5 receptor subtypes. Unlike conventional and other atypical antipsychotics, amisulpride has no affinity for serotonin, α-adrenergic, histamine H1, and cholinergic receptors. It does not bind to sigma sites.
In animal studies, at high doses, amisulpride antagonizes postsynaptic dopamine D2 and D3 receptors, preferentially in the limbic system rather than those in the striatum, thereby reducing dopaminergic transmission. In addition, amisulpride does not induce catalepsy and does not produce D2 hypersensitivity after repeated treatment. At low doses, it enhances dopaminergic neurotransmission by preferentially blocking presynaptic D2/D3 dopamine receptors, producing dopamine release responsible for its disinhibitory effects.
This pharmacological profile explains the clinical efficacy of amisulpride against both negative and positive symptoms of schizophrenia.
Amisulpride's reduced tendency to produce extrapyramidal side effects may be related to its preferential limbic activity.
Pharmacokinetics: In humans, amisulpride shows two absorption peaks: One which is attained rapidly one hour post-dose and a second between 3 and 4 hours after oral administration. Corresponding plasma concentrations are 39±3 and 54±4 ng/mL after a 50 mg dose.
A high-carbohydrate low-fat meal significantly decreases the area under the drug curve (AUC), time to reach maximum concentration (Tmax) and maximum concentration (Cmax) of amisulpride, but no changes were seen after a high-fat meal. The significance of these findings in routine clinical use in not known.
Amisulpride's volume of distribution is 5.8 L/kg. Plasma protein-binding is low (16%) and drug interactions due to displacement are unlikely. The absolute bioavailability of amisulpride is 48%.
Amisulpride is weakly metabolized: two inactive metabolites, accounting for approximately 4% of the dose, have been identified. There is no accumulation of amisulpride and its pharmacokinetics remains unchanged after the administration of repeated doses. Amisulpride is eliminated unchanged in the urine. Amisulpride's elimination half-life (t½) is approximately 12 hrs after an oral dose.
Amisulpride is very weakly dialyzed.
Special Population: Renal Insufficiency: The elimination t½ is unchanged in patients with renal insufficiency while systemic clearance is reduced by a factor of 2.5 to 3. The AUC of amisulpride increased two-fold in mild renal failure and almost tenfold in moderate renal failure. There are no data with doses greater than 50 mg.
Geriatric: Limited pharmacokinetic data in elderly patients (>65 years) showed that a 10 to 30% increase occurs in Cmax, t½, and AUC after a single oral 50 mg dose. No data are available after repeated dosing.
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