Perospirone Hydrochloride Hydrate

Perospirone is a second‐generation antipsychotic classified as a serotonin–dopamine antagonist that is primarily used to treat schizophrenia and bipolar disorder. While its therapeutic effects have been attributed to D 2 and 5‐HT 2A receptor antagonism and partial 5‐HT 1A agonism, its potential interactions with ion channels remain unexplored. In this study, we investigated the effects of perospirone on vascular voltage‐gated K + (Kv) channels in freshly isolated rabbit coronary arterial smooth muscle cells. Perospirone inhibited vascular Kv channels in a concentration‐dependent manner, with a half‐maximal inhibitory concentration (IC 50 ) of 20.54 ± 2.89 μM and a Hill coefficient of 0.92 ± 0.07. Perospirone did not change the activation or inactivation kinetics and did not exhibit use‐dependent inhibition, suggesting that the interaction between the drug and the channels did not affect the voltage sensors or conformational states of the channels. Pretreatment with the Kv2.1 inhibitor guangxitoxin or the Kv7 inhibitor linopirdine did not change the extent of the perospirone‐induced Kv current inhibition, whereas pretreatment with the Kv1.5 inhibitor DPO‐1 partially attenuated the inhibitory effect of perospirone on Kv currents. These findings demonstrate that perospirone inhibits vascular Kv1.5 subtype channels in a concentration‐dependent but use‐independent manner. This previously unrecognized off‐target effect suggests that perospirone can affect vascular function, highlighting its potential cardiovascular implications in clinical settings.

Prolactin elevation associated with antipsychotic use significantly affects medication adherence and long-term treatment outcomes in patients with schizophrenia. The currently available data are insufficient to guide the monitoring and management of elevated prolactin levels in patients on antipsychotic medications. This study aimed to explore the patterns of prolactin level elevation associated with nine second-generation antipsychotics (SGAs) in a real-world setting and compare the associated risks.

This retrospective cohort study utilized data from the inpatient electronic medical records of a large mental health center in China from 2007 to 2019. The study included patients diagnosed with schizophrenia (ICD-10 criteria) who received SGA therapy and whose serum prolactin levels were measured. Exposures were the use of nine specific SGAs (amisulpride, risperidone, paliperidone, ziprasidone, olanzapine, perospirone, quetiapine, clozapine, or aripiprazole), including polytherapy and monotherapy. The primary outcome was incident prolactin elevation in patients during hospitalization. An adjusted stratified Cox proportional hazards regression analysis was used to compare the hazard ratios (HRs) of prolactin level elevation across the nine SGAs. In addition, a dose-response analysis of these SGAs was conducted using the defined daily dose (DDD) method. Dose categories were as follows: < 0.6 DDDs/day (low dose), 0.6 to < 1.1 DDDs/day (medium dose), and ≥ 1.1 DDDs/day (high dose).

This study included 6489 patients with schizophrenia (mean [SD] age, 35.1 [14.2] years; 3396 males [52.3%]). Compared with the nonexposure, amisulpride (HR 2.76, 95% confidence interval [CI] 2.12-3.59), risperidone (HR 2.70, 95% CI 2.30-3.16), paliperidone (HR 1.84, 95% CI 1.37-2.46), and ziprasidone (HR 1.36, 95% CI 1.06-1.76) were associated with the highest risk of prolactin elevation. In contrast, quetiapine (HR 0.73, 95% CI 0.61-0.87), clozapine (HR 0.59, 95% CI 0.46-0.76), and aripiprazole (HR 0.30, 95% CI 0.23-0.37) were associated with the lowest risk. Amisulpride posed the highest risk among male patients, whereas risperidone posed the highest risk among female patients. Different types of dose-response associations were detected in seven SGAs.

This cohort study, conducted in an inpatient setting, identified different risks of prolactin elevation associated with SGAs, along with their dose-response curves. Sex and age must be considered when prolactin elevation is analyzed in patients with schizophrenia who are treated with SGAs.

ClinicalTrials.gov identifier: NCT04002258.