NSAIDs ameliorate cognitive and motor impairment in a model of parkinsonism induced by chlorpromazine

Parkinson's disease [PD] is a long-lasting neurodegenerative brain disease. It is characterized by a gradual decline in motor and non motor symptoms especially postural instability, tremors and memory impairment with localized loss of neurons mainly in the Substantia nigra. In the current research we evaluated the effects of Non-steroidal anti inflammatory drugs [NSAIDs] on motor coordination and memory in chlorpromazine [CPZ] induced Parkinson's experimental model. Intraperitoneal [i.p.] injection of CPZ [3 mg/kg] was given to all rats for 21 days to induce Parkinson like symptoms; ibuprofen [40mg/kg/day] and celecoxib [20mg/kg] were administered 30 minutes after CPZ injection. Behavioral parameters like Catalepsy, muscle strength [wire hanging test], locomotor activity [open field test] were observed. Moreover, its effect on memory was explored by the use of water maze and passive avoidance test. Our results showed CPZ significantly induced motor fluctuation and cognitive impairment in a period of 21 days. Celecoxib and ibuprofen significantly improved cataleptic scores [P<0.01], locomotion and muscular coordination in open field [P<0.01] and in wire hanging test [P<0.01]. Significant improvement in memory was observed with celecoxib [P<0.01] and ibuprofen [P<0.05] in water maze test as well as in passive avoidance test. Therefore, the present study showed neuroprotective and memory enhancing effect of ibuprofen and celecoxib against CPZ induced Parkinson's model

Attenuation of methylphenidate-induced sensitization by co-administration of buspirone

Methylphenidate, which inhibit dopamine transporter is effective in the treatment of ADHD [attention deficit hyperactivity disorder], but long term use of this drug is often associated with addiction and dependence. Locomotor sensitization development to psychostimulants like methylphenidate is an important contributor to drug abuse induced by psychostimulants. Different studies have shown that long term administration of drugs of abuse increases the effectiveness of 5-hydroxytryptamine [5-HT][-1A] somatodendritic receptors. Repeated buspirone administration reduces the effectiveness of 5-HT[1A] somatodendritic receptors. This study was designed to determine that buspirone coadministration may reduce methylphenidate-induced sensitization. The motor activity was compared by using familiar and novel environments after long-term administration of methylphenidate, buspirone and their co-administration. Long term oral administration of methylphenidate at a dose of 2.0mg/kg/day enhanced motor activity in home cage i.e activity of familiar environment monitored at alternate day. Locomotor enhancing effects of methylphenidate were augmented on 13[th] day of drug administration suggesting sensitization induced by the drug. The sensitization effects were significant in home cage monitored on alternate day and also in an open field monitored weekly. Buspirone co-administration at a dose of 10mg/kg/day prevented methylphenidate-induced sensitization. It is suggested that the sensitization development to methylphenidate may oppose by buspirone co-administration due to the reduction in the sensitivity of 5-HT[1A] somatodendritic receptors. These findings may help extend future therapeutics in ADHD

Comparison on hepatotoxicity profile of diclofenac sodium and diclofenac potassium on rabbits

Aim of this study was to determine the clinical hepatotoxicity of diclofertac sodium and of diclofenac potassium, further to evaluate whether these drugs could elicit liver cell destruction and anemia, and which drug is comparatively safer for prolong use. Experimental study. This study was conducted in the Department of Pharmacology; Faculty of Pharmacy, University of Karachi, Duration of study was 30 days. Male 50 rabbits were equally divided into 5 groups, group A was served as control and the group B and C were diclofenac sodium [0.8mg/kg/day and 1.5mg/kg/day], and group D and E were of diclofenac potaasium [0.8mg/kg/day and 1.5mg/kg/day], treated. All the animals were caged in pair in an iron caged with free access to grass and hay of standard diet and tap water for a period of 30 days. At the end of 30 days blood was collected through cardiac puncture from each rabbit and was analyzed to determine the levels of SCOT, SGPT, Bilirubin, ESR and Erythrocyte count. The experimental results suggest that SCOT and SGPT levels were significantly increased in diclofenac sodium treated rabbits after 10 and 30 days [P < 0.01], while diclofenac potassium treated rabbits showed significant result, [P < 0.05] only after 30 days of treatment. The level of bilirubin was significantly increased in diclofenac sodium treated rabbits after 10 days and 30 days [P < 0.01] and diclofenac potassium also showed significant result [P < 0.05] after 30 days treatment. Erythrocyte count decreased in both control and treated rabbits after 10 days but control results are not significant. After 30 days diclofenac sodium showed highly significant decreased count of erythrocytes [P < 0.01] but diclofenac potassium showed only significant results [P < 0.05]. E.S.R values significantly increased in diclofenac sodium and diclofenac potassium treated rabbits after 10 days and 30 days. Our study concluded that as compared to sodium, potassium salt of diclofenac is safer for prolong pain management as the incidence of adverse effects were comparably lower in potassium salt

Oral administration of haloperidol at clinically recommended doses elicits smaller parkinsonian effects but more tardive dyskinesia in rats

The present study was designed to monitor extrapyramidal symptoms [EPS] elicited by the oral administration of haloperidol at clinically recommended doses and to compare it with EPS produced when the drug is injected intraperitoneally at doses used in animal research. Rats injected with haloperidol at a dose of 1 mg/kg daily for 5 weeks exhibited akinesia in an open field and impaired motor coordination. Effects of the drug on motor coordination but not on open field akinesia were attenuated gradually from 2-5 weeks of treatment. Oral administration of haloperidol in drinking water at clinically recommended dose exhibited decreased exploratory activity without producing akinesia. Motor coordination was impaired maximally after 3 weeks and tolerance was developed in the drug induced motor impairment after 5 weeks of treatment. Intensity of vacuous chewing movements [VCMs] and tardive VCMs was greater by oral administration than intraperitoneal injections of haloperidol. The present results showed that oral administration of haloperidol expected to produce sustained effect may result in tolerance in acute parkinsonian like effects but more intensity of tardive dyskinesia. We suggest that drugs which may helpful in alleviating tardive dyskinesia may be more useful if person is on oral drug therapy

Computational study on the geometry optimization and excited - state properties of riboflavin by arguslab 4.0.1

Riboflavin [vitamin B[2]] belongs to a group of respiratory enzymes that occur widely in animals and plants participating in vital oxidation- reduction processes in the body. A computational study was conducted on riboflavin by ArgusLab 4.0.1 to obtain the most active conformation of riboflavin and to analyze its excited-state properties. The best conformation of riboflavin was found to be -199.2173 kcal/mol which is the minimum potential energy calculated by geometry convergence function by ArgusLab software; performed according to Hartree-Fock calculation method. Electronic transition states [ground and excited], were also calculated and visualized by semi-empirical ZINDO method by ArgusLab from which molecular properties such as energies, wave function and dipole moments were established. All the results obtained from geometry optimization and excited-state properties lead us to delineate the active sites with charged groups of riboflavin to interact with the receptors. Such types of investigations are significant for drug -receptor interactions

Assessment of self medication in female university students of pharmacy and medicine- a prevalence study

To evaluate the tendency, incidence, relevant awareness, attitude and practice of self-medication in female students of pharmacy and medicine. Self medication is a common trait in those students who are studying medicine, pharmacy or other health sciences. Socio economic features, lifestyle status and awareness about the indications of the medicine are direct factors that affect the practice of self medication. Observational Comparative Study. The study was conducted in three universities of Karachi, two institutes of pharmacy education and one institute of medical sciences from January 2011 to September 2011. A self-developed, pre-validated questionnaire containing open-ended and close-ended items was used for data collection. 460 female students [age 20-25] enrolled for study after informed consent and knowledge of the study purpose, filled in the questionnaire anonymously. The study based on 460 student shows that self-medication prevails for the OTC medicines [76.27%] and Prescription Only medicines [51.30%]. The use of minerals and vitamins by self medication is 54.5%. The most common reason for self medication shown in 306 count is "previous knowledge of drug use". The students of medical and pharmacy practice self medication to varying degree for both the OTC and Prescription Only medications. The easy access to medications promotes such practice, where as large expense of proper health care plays a pivotal role. This tendency with peril signifies the role of an effective and well regulated pharmaceutical care system with its essential components

comparative study on liver toxicity profile of diclofenac sodium and piroxicam on rabbits

Aim of this study was to determine the clinical hepatotoxicity of diclofenac sodium and of piroxicam, and to evaluate whether these drugs could elicit liver cell destruction and anemia, and which drug is comparatively safer for prolong use. This study was conducted in the department of Pharmacology, Faculty of pharmacy, University of Karachi, Karachi. Duration of study was 30 days. Male 40 rabbits were equally divided into 4 groups, group A was served as control and the group B and C was diclofenac sodium [0.8mg/kg/day and 1.5 mg/kg/day], and group D was of piroxicam [0.31 mg/kg/day] treated. All the animals were caged in pair in an iron caged with free access to grass and hay of standard diet and tap water for a period of 30 days. Diclofenac sodium in 2 different doses 0.8mg/kg/day, 1.5 mg/kg/day and similarly Piroxicam [0.31mg/kg/day] dissolved in drinking water and was given orally for a period of 30 days. Control rabbits were given tap water. At the end of 30 days blood was collected through cardiac puncture from each rabbit and was analyzed to determine the levels of SGOT, SGPT, Bilirubin, ESR and Erythrocyte count. It was found that these drugs can induce severe hepatic damage but the ratio of liver toxicity is different, as evident by the elevation of serum aminotransferases, bilirubin and changes in hematological profile. The experimental results suggest that SGOT and SGPT levels were significantly increased in diclofenac sodium treated rabbits after 10 and 30 days [P> 0.01], while piroxicam treated rabbits showed significant result, [P<0.05] only after 30 days of treatment. The level of bilirubin was significantly increased in diclofenac sodium treated rabbits after 10 days and 30 days [P<0.01] and piroxicam also showed significant result [P<0.05] after 30 days treatment. Erythrocyte count decreased in both control and treated rabbits after 10 days but control results are not significant. After 30 days diclofenac sodium showed highly significant decrease in count of erythrocytes [P<0.01], but piroxicam showed less significant results [P<0.05]. E.S.R values significantly increased in diclofenac sodium and piroxicam treated rabbits after 10 days and 30 days. It can be concluded that diclofenac sodium and piroxicam both can play a role in inducing hepatocellular damage, but a greater increase in liver toxicity was seen in diclofenac sodium treated rabbits rather than piroxicam treated rabbits

Computer aided conformational analysis of sulfonated azo dyes diammonium orange G [C 16H10N2O7S2] [NH4]. 4H2O

The present work describes the conformational analysis of diamomonium orange G [C16H10N2O7S2[NH4]. 4H2O] by using kitaigorodsky function. The minimum potential energy was found to be -0.0099839 at fc1=16o and fc 2=360o

Conformational analysis of [Pd [diethylenetriamine] [guanosine]] [CIO[4]][2]

[Pd [diethylenetriamine] [guanosine]][ClO4] 2 is used for the treatment of tumour. Potential energy calculations are performed to establish structure activity relationship of [Pd [diethylenetriamine] [guanosine]] [ClO4] 2. These calculations indicate that. the drug has allowed conformation in the region of 0 degree to 60 degree, 1600 to 240 degree and at 360 degree. The region of 80 degree to 140 degree and 260 degree to 340-degree rotation is not allowed. The most feasible position for the drug to interact with receptor would be at minimum potential energy in the regions from 0 degree to 60 degree, 160 degree to 240 degree and at 360 degree

Conformational analysis of 2-[alpha-D-lyxofuranosyl] maleimide

2-[alpha-D-Iyxofuranosyl] maleimide is one of the analogues of the alpha anomer of the antitumour antibiotic showdomycin. Conformation of 2-[alpha-D-lyxofuranosyl] maleimide on the basis of potential energy calculation is reported. These calculations indicate that the drug has allowed conformation in the region of omega = 0° to 20°, omega = 80° to 120° and at omega = 360°. The region of omega = 140°-340° is not allowed. The most feasible position for the drug to interact with receptor would be at minimum potential energy in the regions from omega = 0° to 20°, omega = 80° to 120° and at omega = omega = 360°