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Dragica Zendelovska, Kristina Pavlovska, Emilija Atanasovska, Kalina Gjorgjievska and Marija Petrusevska

REFERENCES 1. Shorvon S, Perucca E, Engel J., Jr. The treatment of epilepsy. 3. UK: Wiley-Blackwell West Sussex; 2009. 2. Sruthi A, Tejaswi P, Thanuja N, Sudheer Kumar D, Vivek Sagar V. Simple RP-HPLC method for estimation of diazepam in tablet dosage form. J Pharm Res 2013; 6(1):140-144 3. Eatman FB, Colburn WA, Boxenbaum HG, Posmanter HN, Weinfeld RE, Ronfeld R, Weissman L, Moore JD, Gibaldi M, Kaplan SA. Pharmacokinetics of diazepam following multiple-dose oral administration to healthy human subjects. J Pharmacokinet Biopharm. 1977; (5

Open access

Yaareb J. Mousa and Fouad K. Mohammad

hepatotoxicity: changes induced by selected narcotics. J Pharmacol Exp Therap 221 : 708-714. Janero DR. (1990). Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Radic Biol Med 9 : 515-540. Kalman BA, Kim PJ, Cole MA, Chi MS, Spencer RL. (1997). Diazepam attenuation of restraint stress-induced corticosterone levels is enhanced by prior exposure to repeated restraint. Psychoneuroendocrinol o gy 22 : 349-360. Karadeniz A, Yildirim A, Çelebi F

Open access

Blandina Bernal-Morales, Gabriel Guillén-Ruiz, Jonathan Cueto-Escobedo, Juan Francisco Rodríguez-Landa and Carlos M. Contreras

pages); 9. R. Ravenelle, A. K. Berman, J. La, B. Mason, E. Asumadu, C. Yelleswarapu and S. T. Donaldson, Sex matters: females in proestrus show greater diazepam anxiolysis and brain-derived neurotrophic factor- and parvalbumin-positive neurons than males, Eur. J. Neurosci . (2018) in press; 10. J. Simpson, C. Ryan, A. Curley, J. Mulcaire and J. P. Kelly, Sex differences in baseline and drug-induced behavioural responses in classical behavioural tests, Prog. Neuropsychopharmacol. Biol

Open access

Maria T. Georgieva-Kotetarova and Ivanka I. Kostadinova


During the past decade, evidence has emerged that statins have neuroprotective effects.

AIM: The aim of this study was to investigate the effects of atorvastatin and rosuvastatin on learning and memory in rats with diazepam-induced amnesia.

MATERIAL AND METHODS: Experiments were carried out on 48 white male Wistar rats, divided into 6 groups, each of 8 rats. The experimental animals were treated per os for 14 days with atorvastatin and rosuvastatin in doses of 10 mg/kg and 20 mg/kg body weight, respectively. To induce amnesia diazepam was administered intraperitoneally in a dose of 2.5 mg/kg bw. Cognitive skills of the animals were examined after the induction of amnesia with active avoidance test using autonomic reflex conditioner (shuttle box) and passive avoidance tests (step-through and step down) (Ugo Basile, Italy). The following parameters were assessed: number of conditioned responses (avoidances), number of unconditioned responses (escapes) and number of intertrial crossings in the active avoidance test; latency of reactions was measured in the passive avoidance tests.

RESULTS: We found a significant increase of conditioned responses in atorvastatin treated animals (in a dose of 10 mg/kg bw) in active avoidance training. In the animals treated with rosuvastatin in both doses there was a statistically significant increase of unconditioned responses. In the step-through passive avoidance test there was significant improvement of short-term and long-term memory following administration of atorvastatin (10 mg/kg bw). Rosuvastatin (10 mg/kg bw) preserves long-term memory. In the step-down passive avoidance test, atorvastatin (10 mg/kg bw) and rosuvastatin (10 mg/kg bw and 20 mg/kg bw) preserve long-term memory.

CONCLUSIONS: Atorvastatin (10 mg/kg bw) and rosuvastatin (10 mg/kg and 20 mg/kg bw) improve cognitive functions in rats with diazepam-induced amnesia and preserve longterm memory.

Open access

Nikola M. Stojanović, Pavle J. Randjelović and Niko S. Radulović

NS, Miltojević AB, Randjelović PJ, et al. Effects of methyl and isopropyl N-methylanthranilates from ChoisyaternataKunth (Rutaceae) on experimental anxiety and depression in mice. Phytother Res 2013; 27: 1334-8. 9. Evans JD. Straight forward statistics for the behavioral sciences. Brooks/Cole Pub. Co., Pacific Grove Pacific Grove, 1996: 600. 10. Crestani F, Löw K, Keist R, et al. Molecular targets for the myorelaxant action of diazepam. Mol Pharmaco 2001; l59: 442-5. 11

Open access

Anita Ivosevic, Natasa Miletic, Maja Vulovic, Zoran Vujkovic, Snjezana Novakovic Bursac, Slavko S. Cetkovic, Ranko Skrbic and Milos P. Stojiljkovic


Respiratory failure is the predominant cause of death in humans and animals poisoned with anticholinesterases. Organophosphorus and carbamate anticholinesterases inhibit acetylcholinesterase irreversibly and reversibly, respectively. Some of them contain a quaternary atom that makes them lipophobic, limiting their action at the periphery, i.e. outside the central nervous system. They impair respiratory function primarily by inducing a desensitization block of nicotinic receptors in the neuromuscular synapse. Lipophilic anticholinesterases inhibit the acetylcholinesterase both in the brain and in other tissues, including respiratory muscles. Their doses needed for cessation of central respiratory drive are significantly less than doses needed for paralysis of the neuromuscular transmission. Antagonist of muscarinic receptors atropine blocks both the central and peripheral muscarinic receptors and effectively antagonizes the central respiratory depression produced by anticholinesterases. To manage the peripheral nicotinic receptor hyperstimulation phenomena, oximes as acetylcholinesterase reactivators are used. Addition of diazepam is useful for treatment of seizures, since they are cholinergic only in their initial phase and can contribute to the occurrence of central respiratory depression. Possible involvement of central nicotinic receptors as well as the other neurotransmitter systems – glutamatergic, opioidergic – necessitates further research of additional antidotes.

Open access

Lipták Tomáš, Capík Igor, Ledecký Valent, Nagy Oskar, Kuricová Mária, Tóthová Csilla, Maďari Aladár, Farbáková Jana, Petrovič Vladimír and Horňák Slavomír


The aim of this study was to compare the effects of different premedication protocols followed by a propofol/fentanyl TIVA on cardio-respiratory and hemodynamic changes in twenty-four dogs randomly divided into two groups (AMD-group: medetomidine, atropine and diazepam; AXD-group: xylazine, atropine and diazepam). Cardiorespiratory variables, acid-base indices, quality of sedation, induction, intubation and recovery were recorded throughout the experiment. Significant changes were observed for the pO2 level, which was increased in the AMDgroup from 90 min. (*P< 0.05) to 120 min. (**P< 0.01) of anesthesia. This can be explained by a reduction of the administration rate of propofol/fentanyl TIVA and oxygenation initiated due to excessively deep anesthesia detected by an anesthetsiologist, leading to improved ventilation and increased pO2. The pCO2 (*P < 0.05) reached more preferable values during the first 30 min. and pH (**P< 0.01) was significantly improved within the first 60 min. in the AXD-group thanks to less depressant effects of xylazine. Within the first 30 min. of anesthesia a significant heart rate difference between the groups was accompanied with significantly higher BP (hypertension) in the AXD-group (10 min. ***P< 0.001, 30 min. **P< 0.01). This points to the possibility of atropine application only in the case of a tendency to bradycardia followed by hypotension. It can be concluded that xylazine is a better option for the premedication of a propofol/ fentanyl TIVA in dogs undergoing a prolonged surgical intervention, in spite of the fact that lower sedation scores were attained. We have detected significantly less adverse cardio-respiratory and hemodynamic effects of xylazine, and a shorter recovery time when compared to medetomidine

Open access

Robert Roškar and Marija Dolenc

Determination of Benzodiazepines in Urine Via Benzophenone Derivatives Using Liquid Chromatography-Tandem Mass Spectrometry

The aim of this study was to validate a new method for determining benzodiazepines in urine via their benzophenone derivatives, based on liquid chromatography-tandem mass spectrometry (LC-MS/MS). Selected benzodiazepines were analysed after acid hydrolysis of urine and extraction by ethyl acetate in the presence of an internal standard. Samples were analysed using electrospray ionization LC-MS/MS in a multiple reaction monitoring mode. The chromatographic run time on a reversed phase C18 analytical column was set for 9 min. This method was validated in 21 patients receiving methadone. Benzodiazepines intake was established in two out of three patients. LC-MS/MS results were also compared with the rapid immunoassay and the methods showed good agreement. However, in three cases benzodiazepines were detected by LC-MS/MS, but not by the immunoassay. The sensitivity of the developed LC-MS/MS method is comparable to or even higher than of previously reported methods, which makes it suitable as a confirmatory method.

Open access

Anca Buzescu, Nicoleta Aurelia Cristea, Alexandra Chiriac and C. Chiriță

(4): 278-83. 11. Kuribara H., Stavinoha W., Maruyama Y. Behavioural pharmacological characteristics of honokiol, an anxiolytic agent present in extracts of magnolia bark, evaluated by an elevated plus-maze test in mice. J Pharm Pharmacol., 1998; 50(7):819-26. 12. Rodgers R.J., Shepherd J.K. Influence of prior maze experience on behaviour and response to diazepam in the elevated plus-maze and light/ dark tests of anxiety in mice. Psychopharm., 1993; 113(2):237-42 13. Prunell M., Escorihuela R.M., Fernández-Teruel A., Núnez J

Open access

Yu Chen, Li-ming Fu, Xiu-ying Zhao, Jun Zhao and Zhong-ping Duan

1989;86:1558-1562. 10 Blanc P, Etienne H, Daujat M, Fabre I, Zindy F, Domergue J, et al. Mitotic responsiveness of cultured adult human hepatocytes to epidermal growth factor, transforming growth factor-α and human plasma. Gastroenterology 1992;102:1340-1350. 11 Patel T, Roberts LR, Jones BA, Gores GJ. Dysregulation of liver disease: An overview. Semin Liver Dis 1998;18:105-114. 12 Ono S, Hatanaka T, Miyazawa S, Tsutsui M, Aoyama T, Gonzalez FJ. Human liver microsomal diazepam metabolism using cDNAexpressed cytochrome P