Pharmacokinetics study of extended release formulations of buspirone hydrochloride in Beagle dogs

Objective To evaluate the pharmacokinetics(PK)properties of extended release formulations of buspirone hydrochloride in Beagle dogs.Methods A randomized,two period,two treatment,two sequence crossover bioequivalence study was designed;six healthy Beagle dogs were randomly divided into two groups,each group was orally given buspirone tablets or buspirone extended capsule containing 15 mg buspirone hydrochloride.Blood samples(about 1 mL)were collected in heparinized tubes before dosing and at 0.33,0.67,1,2,3,4,6,8,10,12,18,24 h after administration,and were then immediately centrifuged at 3000 rpm for 15 min.The pharmacokinetics(PK)properties of the drugs were evaluated using the liquid chromatographic-tandem mass spectrometric(LC-MS/MS)method.Results The mean tmax was 4.7,0.8 h and Cmax values was 1.8,6.9 μg·L-1,respectively for the sustained-release test(capsule)and reference formulation(tablet).When compared to the tablets,the residence time of the sustained capsules was dramatically prolonged and Cmax was reduced(P<0.01).The initial release speed was slow and stable.The bioavailability was similar to the common tablets.Conclusions The sustained capsule had showed good pharmacokinetics property of sustained-release in the Beagle dogs.

Effects of Buspirone on Anxiolytic Effects of Magnesium in Male Mice

Anxiolytic-like activity of magnesium chloride has been exhibited in the elevated plus-maze test in mice, in several studies. Buspirone is an anxiolytic psychoactive drug of the azapirone chemical class that is not related to benzodiazepines, unlike most drugs predominately used. The purpose of the present study was to examine interaction between magnesium (Mg) and buspirone as a partial agonist of 5-HT1A receptors in producing anxiolytic-like activity in the elevated plus maze. The anxiolytic-like effect of Mg (50, 100 and 200 mg/kg, orally), buspirone (5 mg/kg, i.p) and its interaction with Mg (50 mg/kg) was evaluated after ten days treatment. Mg given at all doses (50, 100 and 200 mg/kg) and buspirone (5 mg/kg) induced an anxiolytic-like effect significantly increasing the percentage of the time spent in the open arms (%OAT), the percentage of the open arm entries (%OAE) and number of total entries. Percent time spend in open arms was reduced when buspirone coadministered with Mg (50 mg/kg) compared to Mg alone. However, the number of entries did not change significantly. No synergistic interaction (increased time in open arms and number of open arm entries) between Mg and buspirone was observed, in this test, on the contrary, %OAT preserved about buspirone effects and %OAE remained around Mg effect. The obtained data indicate that Mg may act partly via serotonergic receptors due to buspirone’s inhibitory action as a partial agonist of serotonin receptor.

Kinetics Estimation and Polymorphic Transformation Modeling of Buspirone Hydrochloride

In this work, solvent-mediated polymorphic transformation of metastable Form II to stable Form I of Buspirone Hy-drochloride (BUS-HCl) was studied. The polymorphic transformation was monitored using in-situ Raman spectroscopy. The solvent-mediated transformation process is governed by the dissolution of Form II and the nucleation and subsequent growth of Form I. The model parameters for each of these sub-processes were determined with the aid of experimental data including polymorphic fraction in solid phase, solute concentration, and the crystal size distribution. In order to estimate the kinetic parameters, independent seeded batch sets of experiments were conducted, first to estimate the growth rate of Form I, and consequently to estimate the secondary nucleation of Form I and dissolution rate of Form II. The experimental data showed that the secondary nucleation of Form I occurred slightly after the dissolution of Form II was initiated. The estimated parameters for growth, nucleation and dissolution rates were successfully implemented in the population model and validated with the experiments.

Buspirone along with melatonin attenuates oxidative damage and anxiety-like behavior in a mouse model of immobilization stress

AIM: Stress is recognized to precipitate anxiety and related psychological problems characterized by a wide range of biochemical and behavioral changes. The present study was carried out to investigate the protective effects of melatonin and buspirone, and their combination, against six hours immobilization stress-induced, anxiety-like behavioral and oxidative damage in mice. METHOD: Male Laca mice were pre-treated with melatonin(2.5, 5 mg·kg–1), buspirone(5, 10 mg·kg–1), and their combination for consecutive five days. On the 6th day, animals were immobilized for six hours, and thereafter various behavioral tests were performed followed by biochemical tests. RESULTS: Immobilization stress significantly impaired body weight, locomotor activity, and caused anxiety-like behavior, along with increased oxidative damage. Pretreatment with melatonin and buspirone significantly improved the loss in body weight and locomotor activity, attenuated anxiety-like behavior(in both the mirror chamber and plus maze performance tasks), further restored the levels of brain total proteins, and caused antioxidant-like effects, as evidenced by reduced lipid peroxidation, nitrite concentration, and restoration of reduced glutathione and catalase activity, as compared to control animals. In addition, combination of melatonin(2.5, 5 mg·kg–1) with buspirone(5 mg·kg–1) significantly potentiated their protective effects, as compared to their effects individually. CONCLUSION: The present study suggests that melatonin potentiates the beneficial effect of buspirone against immobilization stress-induced, anxiety-like behavioral and oxidative damage in mice possibly by involving a serotonergic mechanism.

Involvement of Serotonergic System and Magnesium on Anxiolytic Effects of Pomegranate in Male Mice

The anxiolytic activities of Punica granatum L. fruit juice (PGFJ) in various validated animal models of anxiety and amnesia have been recently reported in mice. Similarly, anxiolytic-like activity of magnesium chloride has been exhibited in the elevated plus-maze test in mice, in some studies. Buspirone is an anxiolytic psychoactive drug with known effects on 5-HT1A receptors that its action is not related to benzodiazepines. The purpose of the present study was to examine interactions between PGFJ, magnesium (Mg) and buspirone as a partial agonist of 5-HT1A receptors in producing anxiolytic-like activity in the elevated plus maze in mice. The anxiolytic-like effect of PGFJ (5, 10 and 20 ml/kg, orally), buspirone (5 mg/kg, i.p), Mg (50 mg/kg, orally) and their interactions were evaluated after ten days’ treatment. PGFJ given at all doses induced an anxiolyticlike effect significantly increasing the percentage of the time spent in the open arms, and the percentage of the open arm entries, in a dose-dependent manner. Buspirone showed anxiolytic effect after ten days;however, its effect was roughly comparable to the effect of PGFJ 5 ml/kg. Buspirone in combination with PGFJ (5 ml/kg), did produce more effect compared to buspirone alone and nearly in the range of PGFJ 5 ml/kg response. Also, Mg induced an anxiolytic-like effect that was more than effects observed by buspirone 5 mg/kg. However, binary application of buspirone and Mg showed anxiolytic effects more than buspirone, alone. In another group, Mg in combination with PGFJ (5 ml/kg), produced more anxyolitic effects compared to either Mg or PEF alone. It can be concluded that Pomegranate anxyolitic-like effect is dependent on interactions with both GABAergic (related to Mg) and serotonergic (5-HT1A) systems.