Department of Pharmacy
Permanent URI for this collectionhttp://localhost:4000/handle/123456789/1931
Browse
10 results
Search Results
Item Anti-depressant - Like Effect of Novel 5-HT Receptor Antagonist, (4- 3 benzylpiperazin-1-yl) (3-methoxyquinoxalin-2-yl)methanone (6g) in Acute and Chronic Animal Models of Depression(IJPER, 2013-03) Mahesh, R.A novel 5-HT receptor antagonist '6g' with a good log P and pA value identified from a series of compounds synthesized in our laboratory was subjected to forced 3 2 swim test (FST) (1 and 2 mg/kg, i.p) and tail suspension test (TST) (0.5–2 mg/kg, i.p.). Compound 6g significantly reduced the duration of immobility in mice without affecting the base line locomotion. Moreover, 6g (1 and 2 mg/kg, i.p.), potentiated the 5-hydroxytryptophan (5-HTP)-induced head twitch responses in mice and reversed the reserpine-induced hypothermia (RIH) in rats. In interaction studies of 6g with various standard drugs/ligands using FST, 6g (1 mg/kg, i.p.) potentiated the anti-depressant effect of venlafaxine, desipramine and fluoxetine. Moreover, 6g (1 and 2 mg/kg, i.p.) influenced the effect of 8-OH DPAT and harmane as well as reverse the effect of parthenolide by reducing the duration of immobility in FST. However, 6g (1 and 2 mg/kg, i.p.) has no influence on mCPP induced increase in duration of immobility in FST. Furthermore, 6g (1 mg/kg, i.p.) potentiated the effect of bupropion in TST. Chronic 6g treatment attenuated the behavioral anomalies in olfactory bulbectomy (OBX) rats. In conclusion, these various findings reiterated the anti-depressant-like effects of 6g in behavioral models of depression.Item Anti-depressant like Effect of Pimozide in Acute and Chronic Animal Models of Depression(IJPER, 2015-02) Mahesh, R.The hope of developing better antidepressants has stimulated research on 5-HT receptor, capable of producing diverse antidepressant-like 7 behavioral effects. In the current study, the pimozide, a novel 5-HT receptor antagonist, was screened for its antidepressant potential in 7 rodent's behavioral test battery. Psycho-pharmacological investigations involved acute and chronic treatment (14 days) of pimozide in forced swim test (FST), tail suspension test (TST) in mice and olfactory bulbectomy in rats, respectively. Dose response study in mice FST and TST revealed the initial antidepressant-like effect of pimozide (0.5-4mg/kg i.p.). Interaction studies revealed that pimozide (1and 2mg/kg) significantly enhanced the antidepressant action of citalopram and bupropion in mice FST and TST respectively. Reversal of reserpine induced hypothermia (rats) was observed at same dose level. Further, the behavior anomalies exhibited by olfactory bulbectomised rats (OBX) were attenuated by chronic pimozide treatment as observed in open field and hyper-emotionality tests. In conclusion, this behavioural study depicts the antidepressant-like effect of pimozide in rodent's behavioural model.Item Antidepressant-like effect of a novel 5-HT3 receptor antagonist N-(benzo[d] thiazol-2-yl)-3-ethoxyquinoxalin-2-carboxamide 6k using rodents behavioral battery tests(Sage, 2014-09) Mahesh, R.To investigate the antidepressant-like effect of N-(benzo[d] thiazol-2-yl)-3- ethoxyquinoxalin-2-carboxamide 6k, a 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist using rodents behavioral battery tests.Item Anti-depressant like Effect of Pimozide in Acute and Chronic Animal Models of Depression(IJPER, 2015-02) Mahesh, R.The hope of developing better antidepressants has stimulated research on 5-HT receptor, capable of producing diverse antidepressant-like 7 behavioral effects. In the current study, the pimozide, a novel 5-HT receptor antagonist, was screened for its antidepressant potential in 7 rodent's behavioral test battery. Psycho-pharmacological investigations involved acute and chronic treatment (14 days) of pimozide in forced swim test (FST), tail suspension test (TST) in mice and olfactory bulbectomy in rats, respectively. Dose response study in mice FST and TST revealed the initial antidepressant-like effect of pimozide (0.5-4mg/kg i.p.). Interaction studies revealed that pimozide (1and 2mg/kg) significantly enhanced the antidepressant action of citalopram and bupropion in mice FST and TST respectively. Reversal of reserpine induced hypothermia (rats) was observed at same dose level. Further, the behavior anomalies exhibited by olfactory bulbectomised rats (OBX) were attenuated by chronic pimozide treatment as observed in open field and hyper-emotionality tests. In conclusion, this behavioural study depicts the antidepressant-like effect of pimozide in rodent's behavioural model.Item Antidepressant-like effect of a novel 5-HT3 receptor antagonist N-(benzo[d] thiazol-2-yl)-3-ethoxyquinoxalin-2-carboxamide 6k using rodents behavioral battery tests(Sage, 2014-09) Mahesh, R.To investigate the antidepressant‑like effect of N‑(benzo[d] thiazol‑2‑yl)‑3‑ ethoxyquinoxalin‑2‑carboxamide 6k, a 5‑hydroxytryptamine type 3 (5‑HT3) receptor antagonist using rodents behavioral battery tests. Materials and Methods: 6k screening was performed with behavioral assays for depression‑like forced swim test (FST) at several single doses (0.25-4 mg/kg, intraperitoneal injection (i.p.)) to test the potency of 6k, in which 2 and 4 mg/kg doses were found to be most effective and hence, in further behavioral assays including mechanistic model like 5‑hydroxytryptophan (5‑HTP)‑induced head twitches was performed in mice at acute doses of 6k (2 and 4 mg/kg, i.p.). Furthermore, olfactory bulbectomy (OBX), a surgical model‑induced behavioral alterations was performed in rats, and the effect of 6k administered orally (2 and 4 mg/kg, p.o.) after subchronic treatment for 14 days starting from day 15 of postsurgery was examined by percent sucrose preference test and modified open field test (OFT). Results: 6k (1, 2, and 4 mg/kg, i.p.) reduced the immobility time and increased the swimming behavior in FST without affecting the baseline locomotor score showing antidepressant‑like effect. 5‑HTP‑induced head twitch response was potentiated by 6k (2 and 4 mg/kg, i.p.), which indicated rise in the serotonergic neurotransmission in the brain. 6k (2 and 4 mg/kg, p.o.) showed anti‑anhedonia effect by increasing the sucrose consumption and reversed the behavioral alterations when exposed to modified open field in OBX rats after subchronic treatment for 14 days, thus exhibiting antidepressant‑like effect. Conclusion: 6k attenuated the behavioral derangement in rodents‑based behavioral battery tests for depression, indicating antidepressant‑like potential.Item Antidepressant-like activity of (4-phenylpiperazin-1-yl) (quinoxalin-2-yl) methanone (4a), a novel 5-HT3 receptor antagonist: An investigation in behaviour-based rodent models of depression(Wolters Kluwer, 2012-09) Mahesh, R.The present study was designed to investigate the antidepressant potential of (4-phenylpiperazin-1-yl) (quinoxalin-3-yl) methanone (4a), a novel 5-HT3 receptor antagonist, with an optimal log P (2.84) and pA2 value (7.3) greater than ondansetron (6.9) using rodent behavioural models of depression.Item Antidepressant-like effect of novel 5-HT3 receptor antagonist N-n-butyl-3-ethoxyquinoxalin-2-carboxamide (6p): An approach using rodent behavioral antidepressant tests(Wolters Kluwer, 2013) Mahesh, R.The present study was designed to investigate the antidepressant potential of N-n-butyl-3-ethoxyquinoxalin-2-carboxamide (6p), a novel 5-HT3 receptor antagonist in rodent behavioral models of depression.Item Antidepressant-like activity of 2-(4-phenylpiperazin-1-yl)-1, 8-naphthyridine-3-carboxylic acid (7a), a 5-HT3 receptor antagonist in behaviour based rodent models: Evidence for the involvement of serotonergic system(Elsevier, 2013-08) Mahesh, R.The present study was designed to investigate the putative antidepressant-like activity of 7a, a 5-HT3 receptor antagonist, (although indirect evidence of 5-HT3 antagonism) with an optimal log P (3.35) and pA2 value (7.6) greater than ondansetron (pA2 — 6.6) using behavioural tests battery of depression. Acute treatment of 7a (0.5-2 mg/kg, i.p.) in mice produced antidepressant-like effects in forced swim test (FST) and tail suspension test (TST) without affecting the baseline locomotion in actophotometer test in mice. Moreover, the combination of a sub-effective dose of 7a (0.25 mg/kg, i.p.) and fluoxetine (5 mg/kg, i.p.) produced an anti-immobility effect in mouse FST. Pretreatment of mice with p-chlorophenylalanine methyl ester (PCPA; 100 mg/kg, i.p., an inhibitor of serotonin (5-HT) synthesis, for 4 consecutive days) and 1-(m-Chlorophenyl)-biguanide (mCPBG, 10 mg/kg, i.p., a 5-HT3 receptor agonist) prevented the anti-immobility effects of 7a (2 mg/kg, i.p.) in the mouse FST. In addition, 7a (0.5–2 mg/kg, i.p.) treatment also potentiated the 5-hydroxytryptophan (5-HTP) and pargyline induced head twitch response in mice. Furthermore, sub-chronic treatment (14 days) with 7a (0.5–2 mg/kg, i.p.) and paroxetine (10 mg/kg, i.p.) significantly attenuated the behavioural anomalies induced by bilateral olfactory bulbectomy in rats in a modified open field paradigm. These results suggest that the antidepressant-like action of 7a may be mediated by an interaction with the serotonergic system and this molecule should be further investigated as an alternative therapeutic approach for the treatment of depression.Item Effect of a Selective Cyclooxygenase Type 2 Inhibitor Celecoxib on Depression Associated with Obesity in Mice: An Approach Using Behavioral Tests(Springer, 2014-05) Mahesh, R.The biological mechanisms that link the development of depression to metabolic disorders such as obesity and diabetes remain ambiguous. In the present study the potential of a selective cyclooxygenase inhibitor celecoxib (15 mg/kg p.o.) was investigated in depression associated with obesity in mice. Behavioral tests used to assess depressive-like behavior were sucrose preference test, forced swim test (FST), tail suspension test (TST) and elevated plus maze (EPM). The basal locomotor score in obese mice was not altered. Furthermore, estimation of biochemical parameters was performed for plasma glucose, total cholesterol, triglycerides and total proteins. Escitalopram (10 mg/kg p.o.) served as reference standard drug. In the results, chronic treatment with celecoxib for 28 days significantly attenuated the behavioral alterations as indicated by increased the sucrose consumption, reduced the immobility time in FST and TST, increased the percent open arm time and entries in EPM in obese mice. In the biochemical parameters celecoxib significantly reversed the increased plasma glucose, total cholesterol, triglycerides and total proteins in obese mice. In conclusion, celecoxib exhibited potential antidepressant-like effect in depression associated with obesity, which to some extent is mediated by reversing the altered plasma glucose in obese mice.Item Antidepressant-like effect of etazolate, a cyclic nucleotide phosphodiesterase 4 inhibitor—an approach using rodent behavioral antidepressant tests battery(Elsevier, 2012-08) Mahesh, R.Etazolate, a pyrazolopyridine class derivative is selective inhibitor of type 4 phosphodiesterase (PDE4), an enzyme catalyzes the hydrolysis of cyclic nucleotide viz. cAMP & regulates cAMP signal transduction. Enhancing cAMP signal transduction by inhibition of PDE4 is known to be beneficial in depression disorders. Thus, the present study was designed to investigate thoroughly the antidepressant potential of etazolate using rodent behavioral models of depression. Acute treatment of etazolate (0.25–1 mg/kg, i.p.) exhibited antidepressant-like effects in forced swim test (FST) & tail suspension test (TST) in mice without influencing the baseline locomotion in actophotometer test. Interaction studies of etazolate sub-effective dose (0.12 mg/kg, i.p.), were carried out with sub-effective dose of conventional antidepressants like fluoxetine (5 mg/kg, i.p.), venlafaxine (4 mg/kg, i.p.) & desipramine (5 mg/kg, i.p.) in FST. Etazolate at sub-effective dose produced synergistic antidepressant-like effect with conventional antidepressants in the mouse FST. In addition, combined treatment of etazolate & conventional antidepressants had no significant effect on baseline locomotion. Moreover, etazolate (0.5 and 1 mg/kg, i.p.) increased head twitch scores in mice & antagonized the reserpine-induced hypothermia in rats. Chronic treatment (14 days) with etazolate (0.5 and 1 mg/kg, p.o.) & fluoxetine (10 mg/kg, p.o.) significantly reversed the behavioral anomalies induced by bilateral olfactory bulbectomy in rats in modified open field exploration. In conclusion, taken together, our results suggested that etazolate exhibited antidepressant-like activity in acute & chronic rodent models of depression & deserves as a therapeutic tool that could help the conventional pharmacotherapy of depression.