Pharmacokinetics of diclofenac sodium and papaverine hydrochloride after oral administration of tablets to rabbits

Non-compartmental pharmacokinetic analysis of diclofenac sodium (DIC) and papaverine hydrochloride (PAP) after oral administration of composed tablets to rabbits was developed. HPLC method for determination of DIC and PAP in rabbit plasma was developed and validated. Chromatographic separation of DIC, PAP and the IS was achieved on a Zorbax SB C18 5-μm column (150 mm ◊ 4.6 mm) using methanolwater (55 : 45, v/v) as mobile phase at a flow rate of 0.8 mL/min. Pharmacokinetic analysis showed that oral administration of a tablet composed of DIC and PAP do not change the pharmacokinetic parameters such as MRT, MAT, Cl and bioavailability of the active substances compared with single administration of DIC and PAP after single dose

New arylpiperazine derivatives with antidepressant-like activity containing isonicotinic and picolinic nuclei: evidence for serotonergic system involvement

n/

Caffeine enhances the antidepressant-like activity of common antidepressant drugs in the forced swim test in mice

Caffeine is the most widely used behaviorally active drug in the world which exerts its activity on central nervous system through adenosine receptors. Worrying data indicate that excessive caffeine intake applies to patients suffering from mental disorders, including depression. The main goal of the present study was to evaluate the influence of caffeine on animals’ behavior in forced swim test (FST) as well as the effect of caffeine (5 mg/kg) on the activity of six typical antidepressants, such as imipramine (15 mg/kg), desipramine (10 mg/kg), fluoxetine (5 mg/kg), paroxetine (0.5 mg/kg), escitalopram (2 mg/kg), and reboxetine (2.5 mg/kg). Locomotor activity was estimated to verify and exclude false-positive/negative results. In order to assess the influence of caffeine on the levels of antidepressant drugs studied, their concentrations were determined in murine serum and brains using high-performance liquid chromatography. The results showed that caffeine at a dose of 10, 20, and 50 mg/kg exhibited antidepressant activity in the FST, and it was not related to changes in locomotor activity in the animals. Caffeine at a dose of 5 mg/kg potentiated the activity of all antidepressants, and the observed effects were not due to the increase in locomotor activity in the animals. The interactions between caffeine and desipramine, fluoxetine, escitalopram, and reboxetine were exclusively of pharmacodynamic character, because caffeine did not cause any changes in the concentrations of these drugs neither in blood serum nor in brain tissue. As a result of joint administration of caffeine and paroxetine, an increase in the antidepressant drug concentrations in serum was observed. No such change was noticed in the brain tissue. A decrease in the antidepressant drug concentrations in brain was observed in the case of imipramine administered together with caffeine. Therefore, it can be assumed that the interactions caffeine-paroxetine and caffeine-imipramine occur at least in part in the pharmacokinetic phase

Traxoprodil, a selective antagonist of the NR2B subunit of the NMDA receptor, potentiates the antidepressant-like effects of certain antidepressant drugs in the forced swim test in mice

One of the newest substances, whose antidepressant activity was shown is traxoprodil, which is a selective antagonist of the NR2B subunit of the NMDA receptor. The main goal of the present study was to evaluate the effect of traxoprodil on animals’ behavior using the forced swim test (FST), as well as the effect of traxoprodil (10 mg/kg) on the activity of antidepressants, such as imipramine (15 mg/kg), fluoxetine (5 mg/kg), escitalopram (2 mg/kg) and reboxetine (2.5 mg/kg). Serotonergic lesion and experiment using the selective agonists of serotonin receptors 5-HT(1A) and 5-HT(2) was conducted to evaluate the role of the serotonergic system in the antidepressant action of traxoprodil. Brain concentrations of tested agents were determined using HPLC. The results showed that traxoprodil at a dose of 20 and 40 mg/kg exhibited antidepressant activity in the FST and it was not related to changes in animals’ locomotor activity. Co-administration of traxoprodil with imipramine, fluoxetine or escitalopram, each in subtherapeutic doses, significantly affected the animals’ behavior in the FST and, what is important, these changes were not due to the severity of locomotor activity. The observed effect of traxoprodil is only partially associated with serotonergic system and is independent of the effect on the 5-HT(1A) and 5-HT(2) serotonin receptors. The results of an attempt to assess the nature of the interaction between traxoprodil and the tested drugs show that in the case of joint administration of traxoprodil and fluoxetine, imipramine or escitalopram, there were interactions in the pharmacokinetic phase

Bioaccessibility of phenolic compounds, lutein, and bioelements of preparations containing Chlorella vulgaris in artificial digestive juices

Chlorella vulgaris Beijerinck is a spherical, green alga belonging to the genus Chlorella and family Chlorellaceae. It has high nutritional value and shows multiple biological effects. Dietary supplements that contain extracts of C. vulgaris are sold in the form of tablets, capsules, powders, and aqueous solutions. To the best of our knowledge, this is the first study to determine the content of bioelements (zinc, iron, and magnesium), phenolic compounds, and lutein before and after incubation with artificial digestive juices from preparations containing C. vulgaris. In this study, we used commercial preparations in the form of powder and tablets. The samples were incubated in artificial gastric juice and then in artificial intestinal juice for 30 and 90 min. The contents of bioelements were determined by using the flame atomic absorption spectrometric method. Lutein and phenolic compounds were analyzed by high-pressure liquid chromatography. We also aimed to evaluate the quality of chlorellacontaining formulations by using the methods described in the European Pharmacopoeia 8th edition. According to the results, the preparations containing C. vulgaris demonstrated the presence of phenolic compounds and lutein. Therefore, daily supplementation of preparations containing C. vulgaris substantiates its usefulness for humans. The qualitative composition of the examined organic substances and bioelements was found to be in accordance with the manufacturer's declarations on the packaging containing C. vulgaris compared with the control samples; however, the contents of bioelements were found to be negligible after incubation with artificial digestive juices. This shows that the examined preparations containing C. vulgaris are not good sources of bioelements such as zinc, iron, or magnesium

Release of bioactive substances from formulations containing "Arthrospira Platensis (Spirulina Platensis)"

Arthrospira platensis (Spirulina platensis) is a well-known microalga and has been utilized as a medicinal agent and foodstuff by humans since at least 16th century. The aim o f this study was to determine zinc content as well as determine phenolic and indole compounds from commercial preparations containing Arthrospira platensis (lyophilizate, tablets, and capsules) before and after extraction with methanol and incubation with artificial digestive juices. The secondary aim of this study was to evaluate the quality of these preparations. The samples were incubated in artificial stomach juice and in intestinal juice. The samples were mineralized and their zinc(II) ions content was estimated using flame absorption atomic spectroscopy (F-AAS). The maximum zinc(II) ions content released into the digestive juices was found to be up to 1.6 mg/100 g of the preparation. Phenolic compounds identified in the examined extracts are as follows: gallic acid; protocatechuic acid; 3,4-dihydroxyphenylacetic acid; p-hydroxybenzoic acid; syringic acid; cinnamic acid; and quercetin. Furthermore, indole compounds identified were 5-hydroxy-L-tryptophan, 5-methyl-L-tryptophan, L-tryptophan, tryptamine, and 5-methyltryptamine. Consequently, it was also found that the distributed Arthrospira platensis in the form of tablets does not disintegrate in the artificial digestive juices. Among the examined preparations, only hard capsules met the requirements of the European Pharmacopeia 8th ed

Activity and safety of inhaled itraconazole nanosuspension in a model pulmonary Aspergillus fumigatus infection in inoculated young quails

Pulmonary aspergillosis is frequently reported in parrots, falcons, and other birds held in captivity. Inhalation is the main route of infection for Aspergillus fumigatus, resulting in both acute and chronic disease conditions. Itraconazole (ITRA) is an antifungal commonly used in birds, but its administration requires repeated oral dosing, and the safety margin is narrow. To investigate the efficacy of inhaled ITRA, six groups of ten young quails (Coturnix japonica) were inoculated intratracheally with 5 × 10(6) spores (3 groups) or 5 × 10(7) spores (3 groups). Animals were exposed to nebulized ITRA nanosuspension as 10 % suspension or 4 % suspension, once daily for 30 min, starting 2 h after inoculation for 6 days. Control groups were exposed to nebulized saline for the same period of time. Survival and clinical scores were evaluated, and animals were subjected to gross pathology. In control animals, aspergillosis resulted in systemic disease without pulmonary or air sac granulomas. Animals died from multiple organ failure. Inhalation of 10 % ITRA nanosuspension blocked lethality and prevented disease-related symptoms in the quails exposed to the low dose of spores, while the disease course in quails inoculated with the high-spore dose was retarded. Inhalation of 4 % ITRA nanosuspension was less effective. Both inhalations were well tolerated, and gross pathology did not reveal signs of local toxicity. The data indicate that inhaled administration of 10 % ITRA nanosuspension is capable of alleviating an acute A. fumigatus infection in quails. A lower ITRA concentration may be only active in chronic pulmonary aspergillosis

Influence of the CB1 and CB2 cannabinoid receptor ligands on the activity of atypical antidepressant drugs in the behavioural tests in mice

Available data support the notion that cannabinoids, whose therapeutic value is limited due to severe adverse reactions, could be beneficial as adjunctive agents in the management of mood disorders. Polytherapy, which is superior to monotherapy in the terms of effectiveness, usually requires lower doses of the individual components. Therefore, the main objective of our study was to determine whether administration of cannabinoid (CB) receptor ligands would enhance the antidepressant activity of atypical antidepressant drugs, i.e. agomelatine and tianeptine. To evaluate the antidepressant-like potential of the tested combinations, the mouse forced swim test (FST) and the tail suspension test (TST) were used. The HPLC method was applied to assess the brain levels of agomelatine and tianeptine. Both behavioural tests demonstrated that per se an ineffective intraperitoneal dose of oleamide (CB1 receptor agonist, 5 mg/kg) potentiated the anti-immobility activity of tianeptine (15 mg/kg), whereas AM251 (CB1 receptor inverse agonist/antagonist, 0.25 mg/kg) enhanced the antidepressant effects of tianeptine and agomelatine (20 mg/kg). Intraperitoneal co-administration of per se inactive doses of AM630 (CB2 receptor inverse agonist/antagonist) and agomelatine or tianeptine significantly reduced the immobility time of animals only in the FST. CB receptor ligands did not affect the brain levels of the tested atypical antidepressants. In summary, the outcomes of the present study showed that activation and inhibition of CB1 receptors as well as inhibition of CB2 receptors may increase the antidepressant activity of tianeptine, whereas only inhibition of CB1 and CB2 receptors has a potential to augment the antidepressant activity of agomelatine

Ligands of the CB2 cannabinoid receptors augment activity of the conventional antidepressant drugs in the behavioural tests in mice

Although a lot of information can be found on the specific dual role of the endocannabinoid system in the emotional-related responses, little is known whether stimulation or inhibition of the cannabinoid (CB) receptors may affect the activity of the frequently prescribed antidepressant drugs. Our interests have been particularly focused on the potential influence of the CB$_{2}$ receptors, as the ones whose central effects are relatively poorly documented when compared to the central effects of the CB$_{1}$ receptors. Therefore, we evaluated the potential interaction between the CB$_{2}$ receptor ligands (i.e., JWH133 - CB$_{2}$ receptor agonist and AM630 - CB$_{2}$ receptor inverse agonist) and several common antidepressant drugs that influence the monoaminergic system (i.e., imipramine, escitalopram, reboxetine). In order to assess the antidepressant-like effects we used two widely recognized behavioural tests, the mouse forced swim test (FST) and the tail suspension test (TST). Brain concentrations of the tested antidepressants were evaluated by the HPLC method. Intraperitoneal co-administration of per se ineffective doses of JWH133 (0.25 mg/kg) or AM630 (0.25 mg/kg) with imipramine (15 mg/kg), escitalopram (2 mg/kg), and reboxetine (2.5 mg/kg) significantly shortened the immobility time of mice in the FST and the TST, whereas it did not disturb their spontaneous locomotor activity. Furthermore, the brain levels of antidepressants were not changed. Summarizing, the results of the present study revealed that both activation and inhibition of the CB2 receptor function have a potential to strengthen the antidepressant activity of drugs targeting the monoaminergic system. Most probably, the described interaction has a pharmacodynamic background