Cyclizine is a long-established, short-acting drug, registered for preventing motion sickness, post-operative nausea and vomiting (PONV) and 'vomiting of known cause'. The latter is not defined but may include pregnancy and patients receiving palliative care, historically accepted without large, controlled trials. Cyclizine is often described as an 'antihistamine' and sometimes 'anticholinergic', without citing primary literature. Mechanisms of antiemetic activity are poorly understood. We reviewed the published pharmacology of cyclizine with the aim of understanding its mechanism of antiemetic activity. Preclinical/clinical studies were examined and findings interpreted with reference to known mechanisms of nausea and vomiting. Cyclizine antagonizes human H1 receptors and may cause mild drowsiness. Selectivity of action is unclear; therapeutic doses only weakly antagonize muscarinic ACh receptor(s). Motion sickness is ameliorated by H1 antagonism within the vestibular system and associated brainstem nuclei. Mechanisms by which histamine may contribute to PONV are unclear. Perhaps histamine from mast cells and basophils stimulate/sensitize abdominal vagal afferent nerves, synergising with other substances to cause vomiting. Any inhibition of vomiting by cyclizine during pregnancy is not understood; GDF15 is implicated, but relationships with histamine are unclear. Causes of nausea/vomiting during palliative care can be complex, and cyclizine is used without understanding mechanisms. For all indications, it is unclear if nausea is reduced to the same degree as vomiting. There is no consistent evidence to support using cyclizine for vomiting during gastroparesis or chemoradiotherapy. The pharmacology of cyclizine and mechanisms of its antiemetic activity are poorly understood. Testable hypotheses are suggested.

Diphenhydramine and cyclizine are over-the-counter (in many countries) antihistamines that have considerable sedative effects. Therefore, they can be used in drug-facilitated crimes to incapacitate victims. There is a knowledge gap regarding detection possibilities and concentration levels of these antihistamines in hair. This study aimed to investigate whether a single dose of diphenhydramine and cyclizine could be quantified in head hair, and for how long. A single-dose study was conducted in which 12 adult volunteers ingested a single dose of diphenhydramine (25 mg) and cyclizine (44 mg). Hair samples were collected before drug intake and at 1, 3, 5, and if possible, 12 months after intake. To quantify a single dose of antihistamines in head hair, a validated LC-MS/MS method with a lower limit of quantification of 1 pg/mg was applied. Both antihistamines and their main metabolites, N-demethyldiphenhydramine and norcyclizine, were detected in all hair samples collected up to 5 months after intake. Twelve months after intake, diphenhydramine was quantifiable in 25% and cyclizine in 62.5% of available hair samples. The concentrations found in hair within 1 year after intake ranged from 0 to 610 pg/mg for diphenhydramine and from 0 to 590 pg/mg for cyclizine. The median decrease in concentration over 2, 4, and 11 months was 43%, 70%, and 100% for diphenhydramine and 40%, 64%, and 98% for cyclizine. The data obtained provided indicative concentration ranges for a single oral dose of diphenhydramine and cyclizine in hair, thereby improving the interpretation of hair analyses in forensic casework.

Cyclizine is a first-generation H1 antihistamine widely used for the treatment of nausea and motion sickness. In addition to its antiemetic properties, it has anticholinergic and central nervous system effects that may confer psychoactive potential. Although generally regarded as a low-risk medication, increasing evidence suggests a potential for misuse, particularly among adolescents and individuals with mental health disorders or substance-use vulnerabilities. Published data on cyclizine toxicity are limited, and paediatric reports of intentional overdose remain scarce. We report a case of intentional cyclizine overdose in a 14-year-old girl with underlying mental health disorders, highlighting the clinical presentation, management considerations, including serial electrocardiographic assessment, and safeguarding implications. This case underscores the need for increased clinician awareness of cyclizine misuse and its potential harms in the paediatric population.

Gastroparesis is a chronic disorder characterised by delayed gastric emptying in the absence of a physical blockage. Gastroparesis can be clinically classified as mild (Grade 1), moderate (Grade 2), and severe (Grade 3), based on the severity of symptoms, with grade 3 being refractory or intractable symptoms that are not controlled despite medical therapy. Gastroparesis can occur in both type 1 and type 2 diabetes; it is more common in type 1 diabetes. Severe gastroparesis in type 1 diabetes mellitus (T1DM) can be very difficult to manage, especially when accompanied by multi-organ complications. This case highlights the importance of individualised discharge planning for a young adult with severe diabetic gastroparesis, where long hospital stays, difficult-to-treat symptoms, and multiple health problems make it very challenging to achieve quality of life and independence outside the hospital. A 29-year-old patient was admitted to the hospital with severe vomiting due to T1DM-related gastroparesis. Her case was complicated by other comorbidities, such as chronic kidney damage and nephrotic syndrome, persistent hypertension, electrolyte disturbances, and frequent diabetic ketoacidosis. During her long hospital admissions, she was started on multiple antiemetic and prokinetic medications as well as undergoing an invasive procedure of G-POEM (gastric peroral endoscopic myotomy) with no success in symptom management. No improvement was appreciated in gastric emptying studies. Due to difficulty in symptom management and dependency on IV cyclizine, which was the only medication relieving her symptoms, combined with her complex health problems and medical needs, she was compelled to stay in hospital, causing a 14-months-long hospital stay on one occasion, followed by multiple admissions, all due to same reason and a final 4-months stay when multiple multidisciplinary team (MDT) meetings were done to help her live her day-to-day life without being isolated in the hospital and give her a level of autonomy by being discharged on IV cyclizine. This case highlights the importance of an individualised patient care plan when the conventional methods fail to achieve the necessary outcome for young patient's general wellbeing and control over her life without being affected by uncontrolled symptoms, as well as the importance of MDT collaboration, when all the different healthcare professionals come together to ensure the safety of IV home medication is supported by governance and community nursing support.

Postoperative nausea and vomiting (PONV) are frequent complications following general anaesthesia, demanding effective and cost-efficient prophylactic strategies. Therefore, this study aimed to assess the comparative efficacy and safety of ondansetron versus cyclizine for PONV prophylaxis in adult surgical patients by adopting a meta-analysis research approach. The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were adopted in selecting and screening the studies. A computer-based search of the EMBASE, MEDLINE, CENTRAL, and CINAHL databases was carried out using the last search up to November 2025. The risk of bias of the included randomised controlled trials (RCTs) was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool. A sensitivity analysis was performed to assess robustness, and the certainty of evidence was evaluated using Grading of Recommendations Assessment, Development and Evaluation (GRADE). All statistical analyses were performed using MetaAnalysisOnline software. Four RCTs involving 433 adult surgical patients were included. Pooled analysis showed that ondansetron did not significantly reduce the incidence of any PONV compared to cyclizine (odds ratio: 0.74, 95% CI: 0.34 to 1.61, p=0.45). Sensitivity analysis confirmed this finding across surgical subtypes. Additionally, there were no significant differences in the incidence of postoperative vomiting (odds ratio: 1.11, 95% CI: 0.61 to 2.02, p=0.74) or the requirement for rescue antiemetics (odds ratio: 1.83, 95% CI: 0.95 to 3.52, p=0.07). However, moderate heterogeneity was observed (I2=68%) for the primary outcome, and cyclizine was associated with a statistically significant, though clinically small, delay in time to eye opening (mean difference: 2.00 min, p<0.001). The overall certainty of evidence was graded as low to very low. Low-certainty evidence indicates that cyclizine is a reasonable approach to preventing PONV, offering comparable efficacy to ondansetron without prolonging hospital discharge times. Due to its cost-effectiveness and potential specific benefit in diagnostic laparoscopy, it might be useful for ambulatory surgical centres aiming to optimize value-based care. However, the efficacy of cyclizine within modern multimodal protocols has not been consistently determined by these monotherapy trials, and long-term assessments of combined antiemetic strategies need to be evaluated.

In this study, protonation constant values and liquid chromatographic behaviors of hydrophobic cyclizine, chlorcyclizine, hydroxyzine, cinnarizine, cetirizine, meclizine, and buclizine in some water-organic solvent binary mixtures were examined for the first time using classical and green reverse phase liquid chromatography methods. In the isocratic study, the relationship of the retention time and mobile phase pH in water-organic solvent binary mixtures containing acetonitrile (45, 50, 55, 60, 65%, v/v), methanol (60, 65, 70, 75%, v/v) and ethanol (45, 50, 55, 56, 59, 60, 62, 65%, v/v) were determined at 37 °C. In the study, XBridge C18 and Gemini NX C18 columns suitable for the chemical properties of basic compounds were used. The obtained liquid chromatographic data were analyzed using the linear solvation energy relationship methodology and the SOLVER program. The aqueous protonation constant values of the investigated compounds were calculated using the linear relationship between the protonation constant data calculated in studied binary mixtures and some macroscopic constant values of the solvents used. The greenness of methods developed using three different solvents was evaluated with the Analytical Greenness Metric Approach, the Green Analytical Procedures Index, and the Green Solvent Selection Tool approaches.

Cyclizine, an over-the-counter and prescription antihistamine, finds widespread application in the prevention and treatment of motion sickness, encompassing symptoms such as nausea, vomiting, dizziness, along with its effectiveness in managing vertigo. However, the overuse or misuse of cyclizine may lead to hallucinations, confusion, tachycardia, and hypertension. The molecular mechanisms underlying cyclizine-induced cytotoxicity and apoptosis remain unclear. During the 24 h incubation duration, RAW264.7 macrophages were exposed to different concentrations of cyclizine. Cytotoxicity was assessed through the lactate dehydrogenase assay. Flow cytometry employing annexin V-fluorescein isothiocyanate and propidium iodide was utilized to evaluate apoptosis and necrosis. Caspase activity and mitochondrial dysfunction were evaluated through a fluorogenic substrate assay and JC-1 dye, respectively. Flow cytometry employing fluorogenic antibodies was utilized to evaluate the release of cytochrome c and expression of death receptor, including tumor necrosis factor-α receptor and Fas receptor. Western blotting was utilized to evaluate the expression of the Bcl2 and Bad apoptotic regulatory proteins. The findings unveiled from the present study demonstrated that cyclizine exerted a concentration-dependent effect on RAW264.7 macrophages, leading to the induction of cytotoxicity, apoptosis, and necrosis. This compound further activated the intrinsic apoptotic pathway by inducing mitochondrial dysfunction, Bcl2/Bad exchange expression, cytochrome c liberation, and activation of caspases contained caspase 3, 8, and 9. Moreover, the activation of the extrinsic apoptotic pathway was observed as cyclizine induced the upregulation of death receptors and increased caspase activities. Based on our investigations, it can be inferred that cyclizine prompts cytotoxicity and apoptosis in RAW264.7 macrophages in a concentration-dependent manner by triggering both the intrinsic and extrinsic apoptotic pathways.

In this work, we demonstrate a sensitive high-performance liquid chromatography (HPLC) method for the determination of piperazine antihistamine drugs employing innovative electrochemical detection based on a spark-generated nickel oxide nanoparticle-modified carbon fiber microelectrode built into a miniaturized electrochemical detector. The direct carbon fiber-to-nickel plate electrode spark discharge, carried at 0.8 kV DC, with the nickel electrode connected to the negative pole of the high-voltage power supply, provides extremely fast (1 s) in situ tailoring of the carbon fiber microelectrode surface by nickel oxide nanoparticles. It has been found that nickel oxide nanoparticles exhibit an electrocatalytic effect toward the piperazine moiety electrooxidation process, as confirmed by voltammetric experiments, revealing the shift in the peak potential from 1.25 to 1.09 V versus Ag/AgCl. Cetirizine, cyclizine, chlorcyclizine, flunarizine, meclizine, and buclizine were selected as sample piperazine antihistamine drugs, while diclofenac served as an internal standard. The isocratic reversed-phase separation of the above set was achieved within 15 min using an ARION-CN 3 μm column with a binary mobile phase consisting of 50 mM phosphate buffer (pH 3) and methanol (45/55, v/v). The limits of detection (LOD) were within the range of 3.8-120 nM (for cyclizine and buclizine) at E = +1500 mV (vs Ag/AgCl), while the response was linear within the concentration range measured up to 5 μmol L[-1]. The method was successfully applied to the determination of piperazine antihistamine drugs in spiked plasma samples.

Cardiovascular diseases are the primary factor for increased mortality rates around the world. Atherosclerosis brought on by high serum cholesterol can result in coronary heart disease (CHD). The risk of CHD is markedly reduced by lowering serum cholesterol levels. Scientists across the world are inventing new treatment regimens for lowering blood lipid levels. In this work, we repurposed the already established drugs, i.e., cyclizine derivatives as antihyperlipidemic agents. The repurposing was done based on the similarity of the selected cyclizine derivatives with the already established antihyperlipidemic drug, fenofibrate. Computational studies were performed and the 16 cyclizine derivatives docked against PPAR. alpha scored higher than fenofibrate. Lifarizine and medibazine outperform fenofibrate inmmgbsa. Fenofibrate, etodroxizine, meclizine, and cinnarizine had similar mmgbsa scores. The ADME properties of these compounds were performed and from that etodroxizine and levocetirizine were found to have better properties. The computational studies were performed using the Schrodinger software, maestro 12.8. The "Protein Preparation Wizard" module in the Maestro panel was used to create the protein structure and OPLS4 force field was used for energy minimization. The maestro builder panel's "Ligprep", "Receptor Grid Generation" and "Ligand Docking" modules were then used to prepare ligands, receptor grids and to perform docking respectively. MMGBSA was performed on the "prime MMGBSA" segment. Using the "Qikprop" setting in the maestro panel, a number of ADMET properties were predicted, and the program was run in default mode using vsgb as the solvation model.

The classical least squares (CLS) model and three augmented CLS models are adopted and validated for the analysis of pyridoxine HCl (PYR), cyclizine HCl (CYC), and meclizine HCl (MEC) in a quinary mixture with two related impurities: the CYC main impurity, Benzhydrol (BEH), which has carcinogenic and hepatotoxic effects, and the MEC official impurity, 4-Chlorobenzophenone (BEP). The proposed augmented CLS models are orthogonal signal correction CLS (OSC-CLS), direct orthogonal signal correction CLS (DOSC-CLS), and net analyte processing CLS (NAP-CLS). These models were applied to quantify the three active constituents in their raw materials and their corresponding dosage forms using their UV spectra. To evaluate the CLS-based models sensibly, we design a comparative study involving two sets: the training set to construct models and the validation set to assess the prediction abilities of these models. A five-level, five-factor calibration design was established to produce 25 mixtures for the calibration set. In addition, 16 experiments were performed for a test set distributed equally between the in-space and out-space samples. The primary criterion for comparing the models' performance was the validation set's root mean square error of prediction (RMSEP) value. Finally, augmented CLS models showed acceptable results for assaying the three analytes. The results were compared statistically with the reported HPLC methods; however, the DOSC-CLS model proved the best for assaying the dosage forms.