Current Research in Medical Sciences

Activation of Prodrugs Depend on the Metabolism of These Prodrugs

Rezk R. Ayyad — 2026-03-25

Prodrugs depend on enzymatic processes, essentially in the liver, but can also occur in other tissues to release the active metabolite. These metabolic biotransformations are often enzymatically controlled, ensuring the drug becomes pharmacologically active at its site of action. Metabolism may occur at the target site (e.g., in viruses, where drugs are phosphorylated) or in the liver or other tissues. For example, codeine is activated by demethylation to morphine, which is a more active analgesic than codeine. Clopidogrel oxidized to 2-oxoclopidogrel which is active and 2-oxoclopidogrel which is metabolized in two active thiol metabolite. Enalapril is a prodrug that is metabolized to enalaprilat, the active form. L-Dopa is a prodrug that is converted into dopamine in the brain by decarboxylation. Azathioprine is metabolized to mercaptopurine, which is immunosuppressive. Sulfasalazine is a prodrug metabolized by azoreductase and converted to 5-aminosalicylic acid and sulfapyridine, which are more active than sulfasalazine. Prontosil is a prodrug converted into sulfanilamide, which is more active than prontosil. Salicin is a glycoside that is metabolized into salicylic acid, which is active as an analgesic. Valacyclovir is metabolized into acyclovir, which is an active antiviral.

Structural and Functional Neuroimaging in Major Depressive Disorder with Suicidal Ideation: A Review

Xuexia Mao — 2026-03-25

Major depressive disorder with suicidal ideation (MDD-SI) represents a clinically high-risk subtype of depressive disorders characterized by marked neurobiological heterogeneity and has become a major focus of suicide prevention and precision intervention research. In recent years, neuroimaging studies have increasingly demonstrated that patients with MDD-SI exhibit distinct structural and functional brain alterations compared with depressed patients without suicidal ideation. These abnormalities primarily involve the prefrontal–cingulate–limbic system, the default mode network (DMN), and reward-related circuits. With the growing number of longitudinal neuroimaging studies, accumulating evidence suggests that biological treatments—particularly electroconvulsive therapy (ECT)—not only lead to significant reductions in depressive symptoms and suicidal ideation but also induce measurable structural and functional plasticity in these key brain regions and networks.

Structural MRI studies indicate that, at baseline, patients with MDD-SI commonly show gray matter abnormalities in regions such as the anterior cingulate cortex, prefrontal cortex, and hippocampus. Following ECT treatment, regionally selective structural changes have been observed, most notably hippocampal volume increases and structural recovery in the anterior cingulate cortex and ventromedial prefrontal cortex. Functional neuroimaging studies further demonstrate that treatment-related reductions in suicidal ideation are accompanied by enhanced prefrontal–limbic regulatory control, normalization of anterior cingulate cortex function, and suppression of excessive self-referential processing within the DMN. Collectively, these findings suggest that treatment-related neuroimaging changes may constitute an important neural substrate underlying the improvement of suicidal ideation.

This review summarizes current structural and functional neuroimaging findings in patients with MDD-SI before and after treatment, with particular emphasis on treatment-related plasticity in key brain regions and networks. Furthermore, an integrative conceptual framework—linking baseline structural abnormalities, treatment-induced neuroplasticity, and the alleviation of suicidal ideation—is proposed to provide insights for future research on imaging-based predictive biomarkers and the neurobiological mechanisms underlying treatment response.

Research Progress on the Safety of Oliceridine in Perioperative Application

Tianzhong Jia — 2026-03-25

Oliceridine is the first approved biased μ-opioid receptor agonist. It produces analgesia by selectively activating the G protein pathway while minimizing β-arrestin recruitment, a mechanism that theoretically uncouples analgesia from adverse effects. This article systematically reviews the pharmacological basis for the perioperative use of oliceridine, the clinical evidence for its safety, and its value in special patient populations. Studies indicate that at equianalgesic doses, oliceridine is associated with a significantly lower incidence of respiratory depression and better gastrointestinal tolerability compared to conventional opioids. In elderly patients and those with renal or hepatic impairment, no or only mild dose adjustment is required. Cardiovascular and central nervous system adverse effects are manageable, with no risk signals identified beyond those of conventional opioids. Within the framework of multimodal analgesia, oliceridine demonstrates good synergy with other analgesic agents. However, critical questions remain insufficiently addressed, including the risks of long‑term tolerance and dependence, as well as its impact on hard endpoints such as postoperative ileus. Future research should focus on long‑term follow‑up studies and clinical trials centered on bowel function recovery to refine its positioning within Enhanced Recovery After Surgery (ERAS) pathways.