AMIRED 200

Indications

• Schizophrenia
• Other psychoses
• Short-term adjunctive management of psychomotor agitation
• Management of excitement and violent or dangerously impulsive behavior

Dosage

Children: Refer to the BNF for Children for paediatric dosing information.

Adults: Refer to the BNF for specific dosing guidelines; adjustments may be needed based on individual patient factors.

Mechanism of action

Amisulpride acts as a selective antagonist of dopamine D2 and D3 receptors, primarily in the limbic system, which contributes to its antipsychotic effects.

Pharmacodynamics

Amisulpride has a unique profile, demonstrating efficacy in reducing positive symptoms of schizophrenia while having a lower incidence of extrapyramidal side effects compared to first-generation antipsychotics.

Pharmacokinetics

Amisulpride is well absorbed after oral administration, with peak plasma concentrations occurring within 1-3 hours. It undergoes minimal hepatic metabolism and is primarily excreted unchanged in the urine. The elimination half-life is approximately 12 hours.

Contra-indications

• CNS depression
• comatose states
• pheochromocytoma

Adverse effects

• breast abnormalities
• hypersalivation
• increased muscle tone
• decreased alertness
• anxiety
• appetite changes
• confusion
• dyspnea
• hyponatremia
• SIADH
• trismus
• urticaria
• photosensitivity reactions
• postural hypotension (dose-related)
• blurred vision
• thrombocytopenia
• withdrawal syndrome

Interactions

• amisulpride + levodopa: unknown (decreases effects)
• sulphur compounds

Precautions

• start with small doses in severe renal impairment due to increased cerebral sensitivity
• monitor for extrapyramidal symptoms, especially at doses exceeding 6 mg daily

Pregnancy

Caution is advised; refer to specific guidelines.

Breast-feeding

Caution is advised; refer to specific guidelines.

Storage

Store in a cool, dry place away from direct light.

Formulations

• oral suspension
• oral solution
• tablets

Mechanism of action

Dopamine is an essential and critical neurotransmitter produced in the substantia nigra and ventral tegmental regions of the brain. Dopaminergic projection function in the nigrostriatal, mesolimbic, and mesocortical systems. Hyperactive dopamine transmission in the mesolimbic areas, or dopamine dysregulation in various major brain regions, is understood as the key driver of positive and negative symptoms of schizophrenia. Many antipsychotic agents act as D2 receptor antagonists, as with amisulpride. Amisulpride is a selective dopamine D2 and D3 receptor antagonist. It has high preferential activity towards dopamine receptors in the limbic system rather than the striatum, leading to a lower risk of extrapyramidal side effects than other atypical antipsychotic agents. At low doses, amisulpride reduces negative symptoms of schizophrenia by blocking pre-synaptic dopamine D2 and D3 receptors, increasing the levels of dopamine in the synaptic cleft and facilitating dopaminergic transmission. At higher doses, amisulpride blocks postsynaptic receptors, inhibiting dopaminergic hyperactivity: this explains the drug improving positive symptoms. Amisulpride also works as an antagonist at 5-HT_7A receptors and 5-HT_2A receptors, which may be related to its antidepressant effects. The chemoreceptor trigger zone (CTZ), also commonly known as the area postrema (AP), is an important brain region located within the dorsal surface of the medulla oblongata. CTZ is involved in emesis: it contains receptors, such as dopamine receptors, that are activated in response to emetic agents in the blood and relay information to the vomiting center, which is responsible for inducing the vomiting reflex. Amisulpride is an antiemetic agent that works to limit signals that promote nausea and vomiting. Amisulpride binds to D2 and D3 receptors in the CTZ, leading to reduced dopaminergic signalling into the vomiting center.

Pharmacodynamics

Amisulpride is a selective dopamine D2 and D3 receptor antagonist with no affinity towards other dopamine receptor subtypes. Amisulpride is an atypical antipsychotic agent that works as an antagonist at dopamine receptors in the limbic system. Since it works preferentially in the limbic system, amisulpride is less likely to be associated with extrapyramidal adverse effects than other atypical antipsychotic agents. Amisulpride has no affinity for serotonin, alpha-adrenergic, H1-histamine, cholinergic, and sigma receptors. In clinical trials, amisulpride improved reduced secondary negative symptoms, affective symptoms, and psychomotor retardation in patients with acute exacerbation of schizophrenia. Notably, amisulpride has a differential target binding profile at different doses: at low doses, amisulpride selectively binds to presynaptic dopamine autoreceptors. At high doses, it preferentially binds to post-synaptic dopamine receptors. This explains how amisulpride reduces negative symptoms at low doses and mediates antipsychotic effects at high doses. One study alluded that the antinociceptive effects of amisulpride are mediated through opioid receptor acvitation and D2 receptor antagonism. The actions of amisulpride at opioid receptors may explain its pro-convulsant properties. Amisulpride is also an antiemetic agent that prevents and alleviates postoperative nausea and vomiting. It primarily works by blocking dopamine signalling in the chemoreceptor trigger zone, which is a brain area that relays stimuli to the vomiting center. In clinical trials comprising Caucasian and Japanese subjects, amisulpride caused dose- and concentration-dependent prolongation of the QT interval; thus, intravenous infusion under a strict dosing regimen and close monitoring of patients with pre-existing cardiovascular conditions are recommended. Amisulpride increases plasma prolactin levels, leading to an association with benign pituitary tumours such as prolactinoma.