D2/D3 Agonists(Wayne State University)

Dopamine D2/D3 receptor modulation with antipsychotics is thought to affect cognitive function, but causal evidence in humans is scant, and largely limited to single administrations. Clarifying this is of importance given the widespread use of antipsychotics, and to understand the role of D2/D3 signalling in human cognition. We therefore conducted a double-blind, placebo-controlled crossover study following sustained administration of either a dopamine D2/D3 receptor antagonist (amisulpride at 400 mg daily) or a D2/D3 partial agonist (aripiprazole at 10 mg daily) to two separate samples of healthy humans (total n = 50) for 7 days per condition. We assessed cognitive function using a computerised visuospatial working memory (VS-WM) task, and sustained attention and response inhibition using the Sustained Attention to Response Task (SART). We found that both amisulpride and aripiprazole caused impairments in VS-WM function compared to placebo on the Balanced Integration Score (amisulpride: p = 0.0079; aripiprazole: p = 0.015). Both antipsychotics impaired VS-WM performance in terms of response latency (amisulpride: p = 5.5 × 10−7; aripiprazole: p = 0.022), but did not affect response accuracy. Response latency deficits were not correlated with motor impairments induced by either drug, and we also found no effect of either drug on the SART measures, or on subjective alertness, suggesting that D2/D3 antagonism or partial agonism did not cause a generalised cognitive or motor deficit but specifically impaired cognition during VS-WM. This study provides the first causal evidence in healthy humans that working memory function is impaired following either sustained antagonism or partial agonism of D2/D3 receptors by antipsychotic drugs.

Background Schizophrenia is a chronic psychiatric disorder requiring long-term antipsychotic treatment. Cariprazine, a newer atypical antipsychotic with D2/D3 partial agonist activity, has shown promise in managing both positive and negative symptoms. This study aimed to compare the efficacy and safety of cariprazine with olanzapine in patients with schizophrenia in a tertiary care setting in India. Methods A prospective comparative study was conducted among 60 patients diagnosed with schizophrenia, allocated in equal numbers to cariprazine and olanzapine groups. Baseline and six-week assessments were performed using the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms (SANS), and the Udvalg for Kliniske Undersøgelser (UKU) Side Effect Rating Scale. Statistical analyses included t-tests, ANOVA, and chi-square tests, with significance set at p<0.05. Results Both groups showed significant improvements from baseline on BPRS, SAPS, and SANS scores (p<0.001). At six weeks, cariprazine was more effective in reducing negative symptoms (SANS: 39.90 ± 19.25) compared to olanzapine (SANS: 55.37 ± 16.22; p=0.005). Olanzapine led to a greater reduction in positive symptoms (SAPS: 38.13 ± 18.45 vs. 45.80 ± 20.33; p=0.008). UKU scores indicated minimal adverse effects in both groups, with cariprazine showing a slightly more favorable tolerability profile (2.97 ± 3.42 vs. 3.07 ± 3.63; p<0.001). Age significantly influenced BPRS outcomes, while gender, marital status, and socioeconomic status had no significant effect. Conclusion Both cariprazine and olanzapine demonstrated comparable overall efficacy. Cariprazine showed an advantage in improving negative symptoms and exhibited a more favorable side effect profile. Given the small sample size, short follow-up period, and single-center setting, these findings should be interpreted with caution. Larger, long-term trials are needed to confirm the results.