A New Medicine For Schizophrenia

Schizophrenia is a group of complex and severe mental disorders of unknown etiology, affecting 210 million people worldwide, and will continue to rise with population growth and aging. Schizophrenia begins in late adolescence and early adulthood, and its outcome is not optimistic. The symptoms of patients with schizophrenia can be divided into two types. Positive symptoms are easier to control, while negative symptoms are more difficult to improve. It is still a lifelong disease that is difficult to cure.

Introduction

A new medicine for schizophrenia, Lumateperone p-toluenesulfonate, was first developed by Bristol-Myers Squibb. In 2015, Intra-Cellular Therapies obtained a license from BMS for global development. The active ingredient Lumateperone has the activity of serotonin 5-HT2A receptor antagonist in the central nervous system, and acts in combination with the post-synaptic antagonist of CNS dopamine D2 receptors to mediate the effect of glutamate signaling on schizophrenia patients. damage plays an important role. Lumateperone can regulate serotonin by inhibiting the serotonin transporter protein, and acts as a 5-HT2A receptor antagonist for the treatment of behavioral disorders in schizophrenia and other neurological diseases.

Mechanism of action

The pathophysiological mechanisms related to schizophrenia need to be further explored. In patients with schizophrenia, dopamine abnormalities, especially in the prefrontal and mesolimbic regions, have been recognized. In addition, other neurotransmitter abnormalities such as serotonin and glutamate also play a role. According to the target of action of Lumateperone and the binding rate of dopamine D2 receptor, it is the unique performance of the second-generation anti-schizophrenia drug. Different from other antischizophrenic drugs, Lumateperone has partial agonist activity on presynaptic dopamine D2 receptors, which reduces the release of presynaptic dopamine, and also has an antagonistic effect on postsynaptic dopamine D2 receptors. These properties make Lumateperone effective in reducing dopamine signaling.

Adverse reactions

In some cases, patients treated with antipsychotics developed hyperglycemia and diabetes with acidosis, hyperosmolar coma, or death.

The new medicine for schizophrenia can cause adverse changes in blood lipids. Before and after taking antipsychotics, baseline fasting lipids should be measured and monitored regularly during treatment.

Taking new medicine for schizophrenia can increase the body weight of patients. In a clinical trial of adult schizophrenia patients taking Lumateperone capsules and placebo, the baseline body weight of both groups changed, and the body weight increased by ≥7% from baseline to the end of the study.

Patients taking Lumateperone capsules can cause orthostatic hypotension and syncope, and the risk is greatest when taking the drug for the first time. Elderly patients with dehydration symptoms and low blood volume and patients receiving antihypertensive drug treatment at the same time are prone to orthostatic hypotension, and blood pressure monitoring should be strengthened.

Lumateperone capsules can cause drowsiness, orthostatic hypotension, motor and sensory instability, which can lead to falls, fractures, and other injuries.

Lumateperone capsules can cause seizures. Patients with a history of epilepsy or with a lower seizure threshold were at greatest risk. The possibility of lowering the seizure threshold is more common in older patients.

Lumateperone capsules can cause drowsiness and may impair judgment, thinking, and motor skills. In a controlled clinical trial study of 4-6 weeks of short-term administration of Lumateperone capsules and placebo in patients with schizophrenia, the symptoms of somnolence and sedation in the medication group were as follows.

24%, compared to 10% for placebo.

Lumateperone capsules disrupt the body's ability to regulate core body temperature. Strenuous exercise, extreme heat exposure, dehydration, and taking anticholinergic drugs can all increase core body temperature. In this case, patients should take Lumateperone capsules with caution.

Matters needing attention

Mortality increased in Alzheimer's-related psychosis

Patients with Alzheimer's-related psychosis are at increased risk of death when treated with new medicine for schizophrenia. In 17 10-week placebo-controlled clinical trials, the mortality rate was 4.5% in the medication group and 2.6% in the placebo control group, mostly due to cardiovascular or infectious diseases. Lumateperone capsules are not approved for the treatment of dementia-related psychosis.

Increased incidence of cerebrovascular adverse reactions in patients with dementia-related psychosis

Stroke, including fatal stroke and transient cerebral ischemia, occurred in a higher incidence of stroke, including fatal stroke and transient cerebral ischemia, in a placebo-controlled clinical trial of Alzheimer's patients randomized to receive oral formulations of risperidone, aripiprazole, and olanzapine. placebo group.

Antipsychotic malignant syndrome

Antipsychotic malignant syndrome is a potentially lethal syndrome associated with the administration of antipsychotic drugs, with clinical manifestations of hyperthermia, muscle rigidity, delirium, and autonomic instability. Other symptoms include elevated creatine kinase, myoglobinuria with rhabdomyolysis, and acute renal failure. If NMS is suspected, immediately stop taking Lumateperone capsules and strengthen symptomatic treatment and monitoring.

At present, there is no information on the R&D company's application to the State Drug Administration for the import registration certificate of rumperidone capsules, and the research and development of new medicine for schizophrenia needs to be accelerated.