Buspirone (Bus) is an anxiolytic drug and was commercialized forty years ago as an HCl salt. The HCl salt of Bus is also polymorphic, and here, using electron diffraction, we reveal the structure of Bus·HCl Form 2 for the first time. We also prepared the first multicomponent solids of Bus, and describe 15 solids, including cocrystals, an ionic cocrystal, and salts. Significant differences in the solid-state conformation of Bus are described, as well as impacts to the thermal properties upon incorporation into multicomponent solids. Bus, like many drug molecules, does not include a classic ionizable group, which could hamper solid-state development. Bus does include a piperazine ring, one of the five most frequently used nitrogen-based heterocycles in US FDA approved drugs, and is a key site for forming intermolecular hydrogen bonds in each solid. The strategies here could be applied to modify properties in other piperazine-containing drugs.

Selective serotonin reuptake inhibitor (SSRI)-associated bruxism is an increasingly recognized medication-associated phenomenon, although its incidence, neuropharmacologic mechanisms, and optimal management remain incompletely understood. This focused narrative review examines the clinical evidence, proposed mechanisms, and therapeutic implications of SSRI-associated bruxism. Available literature demonstrates recurring temporal associations between SSRI initiation or dose escalation and the emergence of jaw clenching, tooth grinding, pain, and related orofacial symptoms across multiple agents. Proposed mechanisms are multifactorial and may involve altered monoaminergic regulation within central motor networks, including serotonergic-dopaminergic interactions, 5-hydroxytryptamine (serotonin) receptor 1A (5-HT1A) signaling, and possible noradrenergic contributions; however, these mechanisms remain unconfirmed in affected patients. Adjunctive buspirone is the most consistently described pharmacologic strategy and may permit the continuation of an otherwise effective SSRI, although evidence for benefit remains primarily case-based. The literature is limited by heterogeneous bruxism definitions, inconsistent differentiation between awake and sleep manifestations, variable antidepressant exposures, and sparse objective physiologic assessment. Prospective studies using standardized assessment methods and controlled treatment designs are needed to clarify incidence, susceptibility, pathophysiology, and treatment response.

Psychostimulants such as methylphenidate (MPH) and modafinil (MOD) are effective in attention-deficit/hyperactivity disorder and narcolepsy but may induce behavioral activation, anxiety-like responses, and cognitive alterations, particularly under stress. Buspirone (BUS), a nonsedative anxiolytic acting as a partial 5-HT1A receptor agonist, may influence stimulant-related behavioral effects. This study evaluated whether BUS modifies behavioral outcomes induced by chronic MPH and MOD administration in rats exposed to repeated restraint stress. Adult male Sprague-Dawley rats received oral MPH (10 mg/kg), MOD (75 mg/kg), BUS (10 mg/kg), or their combinations for 35 days under restrained or nonrestrained conditions. Behavioral assessments included locomotor activity, exploratory performance (open-field and head-dip tests), and memory evaluation using passive avoidance and Morris water maze paradigms. MPH and MOD alone increased locomotor activity and altered exploratory behavior, with effects influenced by stress conditions. BUS coadministration attenuated stimulant-induced hyperactivity and modulated exploratory responses. BUS alone reduced passive avoidance latency, which may reflect anxiolytic effects rather than impaired memory, while combined treatment indicated modulation of stimulant-associated cognitive outcomes. BUS may reduce stimulant-induced behavioral activation under stress, suggesting its potential as an adjunct to improve the behavioral tolerability of psychostimulant therapy.

Sick sinus syndrome (SSS) presents significant challenges in psychiatric medication management because of the potential for worsening cardiac conduction and interactions with antiarrhythmic therapy. A 35-year-old woman with generalized anxiety disorder (GAD) and insomnia was treated with bupropion, hydroxyzine, melatonin, and intermittent quetiapine, alongside comorbid SSS and supraventricular tachycardia managed post-ablation with metoprolol. A review of her regimen identified several cardiac safety concerns: quetiapine's potential interference with flecainide, hydroxyzine-associated QT prolongation, and bupropion's CYP2D6 inhibition that could increase flecainide levels. Management prioritized minimizing arrhythmogenic risk by discontinuing quetiapine, restricting hydroxyzine to low doses, and continuing melatonin, supplemented by stress testing and reassessment of psychotropic options. This case highlights the importance of careful psychotropic selection in patients with SSS, favoring lower-risk agents, such as mirtazapine, which is one of the safest among several possible alternatives, while maintaining close ECG monitoring and coordinated cardiology and psychiatry collaboration to reduce drug-drug interactions and optimize safety.

Patients with neuropathic pain also experience depression. Although they are treated with various therapies, the effectiveness of these medications is unclear. In the present study, the effect of buspirone on allodynia and depressive-like behavior caused by chronic constriction injury (CCI) of the sciatic nerve, as well as the role of opioid pathways, was investigated. Our findings showed that acute and sub-chronic administration of buspirone (0.3-10 mg/kg) attenuated the mechanical and cold allodynia induced by CCI. In addition, a moderate dose of buspirone (1 mg/kg), but not a high dose (10 mg/kg), reduced the depressive-like behavior induced by CCI. Furthermore, pretreatment with naloxone attenuated the effects of buspirone, whereas co-administration with an ineffective dose of morphine potentiated its action. Also, hippocampal μ-opioid receptor mRNA was decreased, whereas κ-opioid receptor mRNA was increased in CCI mice 14 days after surgery. However, repeated buspirone in CCI-mice mitigated the observed alteration in opioid receptors mRNA expression. In addition, unlike morphine, buspirone did not produce tolerance or withdrawal symptoms following repeated administration. Collectively, these data provide evidence that buspirone can effectively alleviate neuropathic pain and exerts antidepressant-like benefits, potentially through modulation of opioid receptors. Moreover, the effects of buspirone may also be associated with changes in mRNA expression of μ-and κ-opioid receptors in the hippocampus.

Anxiety disorders are among the most common mental health conditions affecting women of reproductive age, and a significant proportion of pregnant women experience clinically relevant anxiety symptoms. In some cases, pharmacological treatment may be required to manage severe or persistent symptoms; however, concerns remain regarding the potential impact of prenatal exposure to anxiolytic medications on fetal brain development. The developing nervous system undergoes critical processes during gestation, including neuronal proliferation, migration, and synaptic formation, which may be sensitive to pharmacological influences. This review examines available clinical and preclinical evidence regarding the neurodevelopmental consequences of prenatal exposure to commonly used anxiolytic medications, especially benzodiazepines (BZDs) and azapirones (AZPs). Evidence from observational human studies has shown associations between prenatal exposure to BZDs and certain neonatal and neurodevelopmental outcomes. However, results remain inconsistent and may be influenced by confounding factors, including maternal psychiatric conditions, co-medication use, and environmental variables. In contrast, data on prenatal exposure to AZPs, especially buspirone, are relatively limited, with most of the available evidence coming from small cohorts and preclinical models. Experimental studies provide mechanistic insights suggesting that early-life exposure to anxiolytic agents may influence neurotransmitter systems, neuronal morphology, and behavioral development in offspring. However, translating findings from animal models to the human clinical context remains challenging. Overall, the current literature highlights substantial knowledge gaps regarding dose-dependent effects, critical developmental windows, and long-term neurobehavioral outcomes. Further well-controlled longitudinal and translational studies are needed to clarify the potential implications of prenatal exposure and to support evidence-based clinical decision-making during pregnancy.

Buspirone is an anxiolytic drug used for the treatment of generalized anxiety disorder. Even though it was patented 50 years ago, it is still among the top three most commonly prescribed anti-anxiety medications in the US. Its fate in the environment and ecotoxic effects have not yet been assessed. In this study, the direct and indirect (with humic acids) photodegradation of buspirone was assessed using the SunTest CPS+ sunlight simulator in two radiation ranges: 280-800 nm and 290-800 nm. The concentration of buspirone and the formation of photoproducts were assessed using liquid chromatography with a diode array and mass spectrometry detector. Toxicity was assessed using biotests with luminescent bacteria and protozoan Spirostomum ambiguum, as well as in silico analyses on daphnia, fish, and protozoan Tetrahymena pyriformis. Buspirone was degraded by sunlight. Expanding the radiation range from 290 to 280 nm accelerated degradation. Humic acids, however, had no effect in either case. The structures of 24 phototransformation products have been proposed. Neither buspirone nor most of its photodegradation products were toxic. Only two derivatives had a calculated 96h-LC50 value for fish below 1 mg L[-1]. The obtained results indicate a low environmental risk of buspirone.

Serotonin (5-hydroxytryptamine [5-HT]) is a key regulator of gastrointestinal function and exerts its effects through a diversity of 5-HT receptors. In the gut, 5-HT is released primarily by enterochromaffin cells, which act as specialized epithelial chemo- and mechanosensors. In humans, 5-HT modulates gastric sensorimotor function, and animal studies suggest that it is involved in enteric neurogenesis. Altered serotonergic signaling is increasingly recognized as an important contributor to the pathophysiology of gastric motility disorders and, therefore, represents an important therapeutic target. Although early serotonergic agents such as cisapride were withdrawn due to safety concerns, newer receptor-specific ligands have become available, broadening the therapeutic landscape and underscoring the need for an updated synthesis of serotonergic pathways and therapies in gastric motility disorders. For the management of gastroparesis, 5-HT4 agonists are the most consistently supported serotonergic agents in international guidelines, with evidence for improving gastric emptying and symptoms, and 5-HT3 antagonists are used primarily for symptomatic control of nausea and vomiting. In functional dyspepsia, serotonergic therapies may be selectively considered for off-label use based on the symptom profile, including mirtazapine (a 5-HT2 antagonist) in patients with early satiety and weight loss, and buspirone (a 5-HT1A agonist) in those with early satiety, postprandial fullness, or bloating. Although selective serotonin reuptake inhibitors and serotonin-noradrenaline reuptake inhibitors are not recommended for use in gastroparesis or functional dyspepsia, their potential role warrants further investigation, particularly given their established efficacy in conditions with chronic pain. Large, controlled trials evaluating the efficacy of serotonergic agents in gastroparesis and functional dyspepsia remain lacking, but recent developments highlight the continued relevance of serotonergic modulation. Recent data on naronapride, a newer 5-HT4 agonist, suggest that more selective agents may offer a clinically relevant benefit, while mitigating cardiovascular safety risks associated with earlier agents. By integrating molecular, physiological, and clinical data, this review aims to clarify the relevance of serotonergic signaling in gastric physiology and motility disorders, define its therapeutic applications, and identify the key remaining evidence gaps.

Shivering is a common complication of targeted temperature management (TTM), which could undermine its neuroprotective benefits by increasing cerebral oxygen consumption and metabolic demand. Buspirone, a 5-HT1A receptor partial agonist, is incorporated into many antishivering protocols for TTM following cardiac arrest, despite limited evidence supporting its efficacy in critically ill patients. We conducted a targeted literature review using PubMed to assess the evidence in favor of the use of buspirone in antishivering protocols during TTM. Experimental, physiological, and clinical studies were reviewed with emphasis placed on study design, patient population, and relevance to critically ill individuals undergoing TTM. Experimental studies in animals and healthy human volunteers show that buspirone can modestly lower core temperature or shivering thresholds. Two small studies (n = 8 each) in healthy male volunteers demonstrated that buspirone reduced the shivering threshold by approximately 0.7°C. A retrospective cohort study (n = 131) in post-cardiac arrest patients showed a reduction in shivering with a multidrug protocol including buspirone, but the independent contribution of buspirone could not be isolated. No randomized controlled trials have evaluated buspirone's efficacy as a standalone antishivering agent in critically ill patients. Current evidence to support the buspirone's use in antishivering protocols is limited and largely extrapolated from noncritical care settings. Given that most patients undergoing TTM already receive sedatives and analgesics with more potent antishivering effects, the incremental benefit of buspirone remains unproven. Furthermore, it adds to the already high burden of polypharmacy in ICU patients and could, in theory, increase the risk of serotonin syndrome. Randomized trials comparing protocols with and without buspirone are needed to determine its clinical utility.