The efficacy and tolerability of pharmacologically active interventions for alcohol-induced hangover symptomatology: a systematic review of the evidence from randomised placebo-controlled trials.

AIMS: To compare quantitatively the efficacy and tolerability of pharmacologically active interventions in the treatment and prevention of alcohol-induced hangover. METHODS: Systematic review of placebo-controlled randomised trials in healthy adults that evaluated any pharmacologically active intervention in the treatment or prevention of hangover. We searched Medline, Embase, PsycINFO and CENTRAL from database inception until 1 August 2021. The primary efficacy outcome was any continuous measure of overall hangover symptoms and the primary tolerability outcome the number of people dropping out because of adverse events (AEs). Quality was assessed using the Grading of Recommendations Assessment Development and Evaluation (GRADE) framework. RESULTS: A total of 21 studies were included reporting on 386 participants. No two studies reported on the same intervention; as such, meta-analysis could not be undertaken. Methodological concerns and imprecision resulted in all studied efficacy outcomes being rated as very low quality. When compared with placebo, individual studies reported a statistically significant reduction in the mean percentage overall hangover symptom score for clove extract (42.5% vs 19.0%, P < 0.001), tolfenamic acid (84.0% vs 50.0%, P < 0.001), pyritinol (34.1% vs 16.2%, P < 0.01), Hovenia dulcis fruit extract (P = 0.029), L-cysteine (P = 0.043), red ginseng (21.1% vs 14.0%, P < 0.05) and Korean pear juice (41.5% vs 33.3%, P < 0.05). All studied tolerability outcomes were of low or very low quality with no studies reporting any drop-outs because of AEs. CONCLUSIONS: Only very low quality evidence of efficacy is available to recommend any pharmacologically active intervention for the treatment or prevention of alcohol-induced hangover. Of the limited interventions studied, all had favourable tolerability profiles and very low quality evidence suggests clove extract, tolfenamic acid and pyritinol may most warrant further study.

Highly sensitive voltamperometric determination of pyritinol using carbon nanofiber/gold nanoparticle composite screen-printed carbon electrode.

A novel and highly sensitive electrochemical method for the detection of pyritinol in pharmaceutical products and serum samples has been accomplished based on voltamperometric response of pyritinol in carbon nanofiber-gold nanoparticle (CNF-GNP)-modified screen-printed carbon electrode (SPCE). The electrochemical response of pyritinol to CNF-GNP-modified SPCE was studied by cyclic voltammetry and square-wave voltammetry (SWV). Under optimized working conditions, the novel sensor shows excellent voltamperometric response toward pyritinol. The SWV study shows significantly enhanced electrochemical response for pyritinol in CNF-GNP-modified SPCE providing high sensitivity to the novel sensor for pyritinol detection. The peak current for pyritinol is found to be linear with the concentration in the range 1.0×10-8-5.0×10-5 M with a detection limit of 6.23×10-9 M using SWV as the detection method. The viability of the new developed sensor for the analytical purposes was studied by performing experiments on various commercial pharmaceutical products and blood serum samples, which yielded adequate recoveries of pyritinol. The novel electrochemical sensor provides high sensitivity, enhanced selectivity, good reproducibility and practical applicability.

Vinpocetine and pyritinol: a new model for blood rheological modulation in cerebrovascular disorders­a randomized controlled clinical study.

Blood and plasma viscosity are the major factors affecting blood flow and normal circulation. Whole blood viscosity is mainly affected by plasma viscosity, red blood cell deformability/aggregation and hematocrit, and other physiological factors. Thirty patients (twenty males + ten females) with age range 50-65 years, normotensive with history of cerebrovascular disorders, were selected according to the American Heart Stroke Association. Blood viscosity and other rheological parameters were measured after two-day abstinence from any medications. Dual effects of vinpocetine and pyritinol exhibit significant effects on all hemorheological parameters (P < 0.05), especially on low shear whole blood viscosity (P < 0.01), but they produced insignificant effects on total serum protein and high shear whole blood viscosity (P > 0.05). Therefore, joint effects of vinpocetine and pyritinol improve blood and plasma viscosity in patients with cerebrovascular disorders.

The protective effects of Cyperus rotundus on behavior and cognitive function in a rat model of hypoxia injury.

CONTEXT: Hypoxia injury (HI) with its long-term neurological complications is one of the leading causes of morbidity and mortality in the world. Currently, the treatment regimens for hypoxia are aimed only at ameliorating the damage without complete cure. The need, therefore, for novel therapeutic drugs to treat HI continues. OBJECTIVE: This study investigates the protective effects of the ethanol extract of Cyperus rotundus L. (Cyperaceae) (EECR), a medicinal plant used in Ayurvedic traditional medicine against sodium nitrite-induced hypoxia in rats. MATERIALS AND METHODS: We have evaluated the protective effect of 200 and 400 mg/kg of EECR against sodium nitrite-induced hypoxia injury in rats by assessing the cognitive functions, motor, and behavioral effects of EECR treatment along with the histological changes in the brain. By comparing the protective effects of standard drugs galantamine, a reversible cholinesterase inhibitor and pyritinol, an antioxidant nootropic drug against sodium nitrite-induced hypoxia in rats, we have tested the protective ability of EECR. RESULTS: EECR at doses of 200 and 400 mg/kg was able to protect against the cognitive impairments, and the locomotor activity and muscular coordination defects, which are affected by sodium nitrite-induced hypoxia injury in rats. CONCLUSION: Based on our results, we suggest that the medicinal herb C. rotundus possesses a protective effect against sodium nitrite-induced hypoxia in rats. Further studies on these protective effects of EECR may help in designing better therapeutic regimes for hypoxia injury.

[Developmental dysphasia: assessment of the drug treatment efficacy].

To assess the efficacy of treatment with encephabol, we examined 40 children, aged from 3 to 5 years, with developmental dysphasia. All patients were randomized into two equal groups: group 1 received encephabol (suspension form, daily dosage 200-250 mg, or 12-15 mg/kg) during 2 months; group 2 did not receive this medication. In the first group, there was a significant improvement of expressive and impressive speech and speech attention; the active vocabulary and a number of phrases in colloquial speech increased by a factor of 3 versus 1.5 in the control group. After the treatment with encephabol, the parents reported the decrease in motor disturbances, psychosomatic disorders, the improvement of attention and the emotional state of the children.

[Efficacy of cortexin in the treatment of memory disorders in children].

Children, aged from 7 to 12 years, with memory disorders were treated with cortexin (30 patients) and encephabol (30 patients). The comparative evaluation of efficacy and safety of these drugs was carried out. The higher cortexin efficacy (the improvement in 86.7% of cases) in comparison with encephabol (the improvement in 63.3% of cases) confirmed by the data of neuropsychological and neurophysiological research is established.

[Encephabol in the treatment of cognitive disorders in epilepsy].

Cognitive disorders in patients with epilepsy were studied before and after the 6-week treatment with encephabol. The data on the examination of 24 patients were summarized. Before the treatment, patients with epilepsy demonstrated a larger number of errors, lower speed of reading and worse learning of the content compared to the controls (18 healthy people). Encephabol was prescribed in dosage 600 mg/day to people over 12 years of age and in dosage 300-400 mg/day to people younger than 12 years. The statistically significant improvement of the global self-rating of cognitive functions, speed of reading, decrease of errors as well as learning of the content were seen after the end of treatment. The improvement of cognitive traits was correlated with the improvement of computed EEG parameters (the decrease of delta power in the right temporal and frontal regions). Encephabol did not lead to the increase of epileptiform activity in the EEG. No increase in the number and severity of seizures was noted. In conclusion, encephabol may be used in treatment of cognitive disorders in epilepsy.

Pyritinol for post asphyxial encephalopathy in term babies-- a randomized double-blind controlled trial.

OBJECTIVE: To evaluate the efficacy of pyritinol in improving the neurodevelopmental outcome at one year of age among term babies with post-asphyxial encephalopathy. SETTING: Level II Neonatal Nursery and Child Development Centre, Medical College, Thiruvananthapuram. DESIGN: Randomised placebo controlled double blind trial. PARTICIPANTS: 108 term babies with post-asphyxial encephalopathy, stratified into three grades based on clinical criteria. INTERVENTION: The treatment group (n=54) received pyritinol and the control group (n=54) received placebo, in exactly the same increasing dosage schedule of 1 to 5 mL liquid drug (20-100 mg) from 8th postnatal day until the end of six months. OUTCOME VARIABLES: Mean Mental Development Index (MDI) and mean Psychomotor Development Index (PDI) measured on Bayley Scales of Infant Development at one year of age. RESULTS: No statistically significant difference was observed in MDI or PDI scores at one year between the treatment and control groups. The confidence interval for the differences ranged from -6.3 to 8.7 for MDI and from - 4.1 to 12.7 for PDI. On multiple regression analysis using one year MDI and PDI scores, even after controlling for birthweight, there was no statistically significant difference between the treatment and control groups. CONCLUSION: Pyritinol is not useful in improving the neurodevelopmental status of babies with post-asphyxial encephalopathy at one year of age.

Stability-indicating chemometric methods for the determination of pyritinol dihydrochloride.

Three multivariate calibration methods, including classical least square with nonzero intercept (CLS), principal component regression (PCR) and partial least square (PLS), have been used for the determination of pyritinol dihydrochloride in the presence of its degradation product. The CLS, PCR and PLS techniques are useful in spectral analysis because the simultaneous inclusion of many spectral wavelengths instead of the single wavelength used in derivative spectrophotometry has greatly improved the precision and predictive abilities of these multivariate calibrations. A training set was constructed for the mixture and the best model was used for the prediction of the concentration of the selected drug. The proposed procedures were applied successfully in the determination of pyritinol dihydrochloride in laboratory-prepared mixtures and in commercial preparations. Pyritinol dihydrochloride was analysed with mean accuracies 99.99 +/- 0.905, 99.91 +/- 0.966 and 99.92 +/- 0.962 using the CLS, PCR and PLS methods respectively. The validity of the proposed methods was assessed using the standard addition technique. The proposed procedures were found to be rapid and simple and required no preliminary separation. They can therefore be used for the routine analysis of pyritinol dihydrochloride in quality-control laboratories.

Pyritinol reduces nociception and oxidative stress in diabetic rats.

The purpose of this study was to assess the antinociceptive and antiallodynic effect of pyritinol as well as its possible mechanism of action in diabetic rats. Streptozotocin (50 mg/kg) injection caused hyperglycemia within 1 week. Formalin-evoked flinching was increased in diabetic rats as compared to non-diabetic rats. Oral acute administration of pyritinol (50-200 mg/kg) dose-dependently reduced flinching behavior in diabetic rats. Moreover, prolonged administration of pyritinol (12.5-50 mg/kg, every 2 days for 2 weeks) reduced formalin-induced nociception. 1H-[1,2,4]-oxadiazolo [4,3-a] quinoxalin-1-one (ODQ, a guanylyl cyclase inhibitor, 2 mg/kg, i.p.), but not naltrexone (a non-selective opioid receptor antagonist, 1 mg/kg, s.c.) or indomethacin (a non-selective cycloxygenase inhibitor, 5 mg/kg, i.p.), blocked the pyritinol-induced antinociception in diabetic rats. Given alone ODQ, naltrexone or indomethacin did not modify formalin-induced nociception in diabetic rats. Oral acute (200 mg/kg) or prolonged (25 mg/kg, every 2 days for 2 weeks) administration of pyritinol significantly reduced streptozotocin-induced changes in free carbonyls, dityrosine, malondialdehyde and advanced oxidative protein products. Four to 8 weeks after diabetes induction, tactile allodynia was observed in the streptozotocin-injected rats. On this condition, oral administration of pyritinol (50-200 mg/kg) reduced tactile allodynia in diabetic rats. Results indicate that pyritinol is able to reduce formalin-induced nociception and tactile allodynia in streptozotocin-injected rats. In addition, data suggest that activation of guanylyl cyclase and the scavenger properties of pyritinol, but not improvement in glucose levels, play an important role in these effects.

Stability-indicating electrochemical methods for the determination of meclophenoxate hydrochloride and pyritinol dihydrochloride using ion-selective membrane electrodes.

The construction and electrochemical response characteristics of polyvinyl chloride (PVC) membrane sensors for the determination of meclophenoxate hydrochloride (I) and pyritinol dihydrochloride (II) in presence of their degradation products are described. The sensors are based on the use of the ion-association complexes of (I) and (II) cation with sodium tetraphenyl borate and ammonium reineckate counteranions as ion-exchange sites in the PVC matrix. In addition beta-cyclodextrin (beta-CD) membranes were used in the determination of I and II. These ion pairs and beta-CD were then incorporated as electroactive species with ortho nitrophenyl octyl ether (oNPOE) as a plasticizer. Three PVC sensors were fabricated for each drug, i.e. meclophenoxate tetraphenyl borate (meclo-TPB), meclophenoxate reineckate (meclo-RNC) and meclophenoxate beta-cyclodextrin (meclo-beta-CD), and the same was done for pyritinol (pyrit-TPB), (pyrit-RNC) and (pyrit-beta-CD). They showed near Nernestian responses for meclophenoxate over the concentration range 10(-5)-10(-2) with slopes of 52.73, 51.64 and 54.05 per concentration decade with average recoveries of 99.92+/-1.077, 99.96+/-0.502 and 100.03+/-0.763 for meclo-TPB, meclo-RNC and meclo-beta-CD respectively. Pyritinol also showed near Nernestian responses over the concentration range of 3.162 x 10(-6) - 3.162 x 10(-4) for pyrit-TPB and pyrit-RNC, and 10(-6) - 3.162 x 10(-4) for pyrit-beta-CD with slopes of 30.60, 31.10 and 32.89 per concentration decade and average recoveries of 99.99+/-0.827, 100.00+/-0.775 and 99.99+/-0.680 for pyrit-TPB, pyrit-RNC and pyrit-beta-CD respectively. The sensors were used successfully for the determination of I and II in laboratory prepared mixtures with their degradation products, in pharmaceutical dosage forms and in plasma.

Stability-indicating methods for determination of pyritinol dihydrochloride in the presence of its precursor and degradation product by derivative spectrophotometry.

A first-derivative spectrophotometric (1D) method and a derivative-ratio zero-crossing spectrophotometric (1DD) method were used to determine pyritinol dihydrochloride (I) in the presence of its precursor (II) and its degradation product (III) with 0.1N hydrochloric acid as a solvent. Linear relationships were obtained in the ranges of 6-22 microg/mL for the (1D) method and 6-20 microg/mL for the (1DD) method. By applying the proposed methods, it was possible to determine pyritinol dihydrochloride in its pure powdered form with an accuracy of 100.36 +/- 1.497% (n = 9) for the (1D) method and an accuracy of 99.92 +/- 1.172% (n = 8) for the (1DD) method. Laboratory-prepared mixtures containing different ratios of (I), (II), and (III) were analyzed, and the proposed methods were valid for concentrations of < or = 10% (II) and < or = 50% (III). The proposed methods were validated and found to be suitable as stability-indicating assay methods for pyritinol in pharmaceutical formulations.

[Efficiency of encefabol use in patients with dyscirculatory encephalopathy]. / Effektivnost' lecheniia éntsefabolom bol'nykh distsirkuliatornoi éntsefalopatiei.

The article presents the findings of the Encefabol treatment of 50 patients aged 56-68 yy with vascular encephalopathy at the I-III stage, caused by atherosclerotic and high blood pressure pathological processes. The individual dose prescription of the medication to patients with vascular encephalopathy was substantiated in the article. The importance of psychodiagnostic tests in assessment of Encefabol treatment efficiency of the disease was shown in the article.

[Cognitive disturbances in patients with tics and Tourette's syndrome and their correction with encephabol]. / Kognitivnye narusheniia u bol'nykh s tikami i sindromom Turetta i ikh korrektsiia éntsefabolom.

Ninety-four patients with tick hyperkinesis (57) and Tourette's syndrome (37) were studied. Neuropsychological examination revealed memory, attention and audio-motor disturbances and symptoms of dysgraphia and dyslexia. Cognitive impairment may develop before ticks appearance and aggravate during hyperkinesis exacerbation. In the patients with Tourette's syndrome, cortical dysfunctions were mostly pronounced. These cognitive disturbances correlated with the indices of spectral analysis of bioelectrical brain activity in frontal and temporal areas. In 83 patients, an efficacy of encephabol treatment combined with basic therapy was studied. Encephabol given in dosage 200-300 mg daily to patients aged 5-7 years and 600 mg--to those aged over 7 years during 6 weeks significantly improved memory, attention and praxis function.

[Current strategies of pathogenetic therapy of Alzheimer's disease]. / Sovremennye strategii patogeneticheskoi terapii bolezni Al'tsgeimera.

This is a review of the data available in the literature and the authors' own findings on pathogenetical rationale for the use and clinical study of current treatments for Alzheimer's disease (AD) (synonym: Alzheimer-type dementia). In the past decade many attempts have been made at targeting different links of the pathogenesis of a neurodegenerative process that underlie AD. Several areas of pathogenetical therapy for AD have been developed on the basis of experimental studies and pilot clinical tests. The most developed areas are as follows: various compensatory (replacement) treatments aimed at overcoming neurotransmitter deficit in different neuronal systems that are damaged in AD to a greater or lesser extent; neuroprotective therapy promoting increased viability (survival) of neurons and their plasticity, and vasoactive therapy. Rather new directions of AD pathogenetic therapy, such as antiinflammatory and hormonal therapy along with antiamyloid therapeutic strategies are still under study.

Acute pancreatitis due to pyritinol: an immune-mediated phenomenon.

A 23-year-old man experiencing three episodes of acute pancreatitis of undetermined etiology is described. Repeated questioning revealed that all three events had occurred after intake of the drug pyritinol. Controlled rechallenge with a single dose of the drug led to a fourth episode of acute pancreatitis. Skin testing was negative, but lymphocyte stimulation tests and double fluorescence analysis detected pyritinol-activated CD4 and CD8 lymphocytes. Together with the clinical observation that the intervals between drug intake and start of symptoms of acute pancreatitis became shorter with repeated exposure, the data are consistent with an immune-mediated origin of the pancreatitis. Pyritinol has to be added to the list of drugs capable of inducing acute pancreatitis.

Event-related potentials and psychopharmacology. Cholinergic modulation of P300.

The event-related potential P300 probably reflects the encoding of information into short-term memory. Anatomical structures of the limbic system are involved in this process. Since the same structures are involved in the generation of the event-related potential P300, P300 is thus well suited to assess pharmacological influence on memory functions and cognitive processes, for example, by changing the availability of neurotransmitters like acetylcholine at their respective receptors.