Radhakrishnan Mahesh

Radhakrishnan Mahesh
Birla Institute of Technology and Science Pilani | BITS Pilani · Department of Pharmacy

M.Pharm., Ph.D.

About

118
Publications
11,749
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1,872
Citations
Additional affiliations
July 1989 - present
Birla Institute of Technology and Science Pilani
Position
  • Professor and Dean Faculty Affairs
July 1989 - July 2015
BITS Pilani
Position
  • Professor (Full)-Current

Publications

Publications (118)
Chapter
Depression is a chronic and debilitating mental disorder that often remains undertreated. It could be due to unclear understanding of pathophysiology and/or inconsistent efficacy of current pharmacotherapy. Since the discovery of the first effective medications in the late 1950s, a variety of agents have been developed, which are mainly based on co...
Article
The prokaryotic ATP-dependent ClpP protease, localized in the relict plastid of malaria parasite, represents a potential drug target. In the present study, we utilized in silico structure-based screening and medicinal chemistry approaches to identify a novel pyrimidine series of compounds inhibiting P. falciparum ClpP protease activity and evaluate...
Article
Introduction: Obesity is an important risk factor for depression as more than half of the obese population is susceptible for depression at double rate. Our earlier studies reported the antidepressant potential of 5-HT3 receptor antagonist, ondansetron (OND) in depression associated obesity using behavioral tasks. The present research work is aime...
Article
Full-text available
RationaleDepression associated with obesity remains an interesting area to study the biological mechanisms and novel therapeutic intervention. Objectives The present study investigates the effect of a novel 5-HT3 receptor antagonist 3-methoxy-N-p-tolylquinoxalin-2-carboxamide (QCM-4) on several pathogenic markers of depression associated with obesi...
Article
Traumatic brain injury (TBI) is one of the leading cause of psychiatric conditions in patients, amongst which, depression and anxiety are more frequent. Despite the preclinical antidepressant-like effects, clinical development of Phospodiesterase-4 (PDE4) enzyme inhibitors has been hampered due to serious side effect profiles, such as nausea and vo...
Article
Background & objectives Alteration in the serotonin leads to the psychological illness, such as depression, anxiety, schizophrenia, eating disorders, obsessive-compulsive disorder, panic disorders and migraines. The objective of the current study was to investigate the antidepressant and anxiolytic activities of N-(pyridin-3-yl) quinoxalin-2-carbox...
Article
Background: 5-HT3 receptor antagonists play a key role in the management of psychiatric disorders such as, depression and anxiety. They may act through modulation of serotonergic transmission. In the present study, a novel and potential 5-HT3 receptor antagonist, 6g (4-benzylpiperazin-1-yl)(3-methoxyquinoxalin-2-yl) methanone, which exhibited good...
Article
Full-text available
Pioglitazone, a peroxisome proliferator activated receptor gamma (PPARγ) agonist belonging to thiazolidinedione class, is mainly used in diabetes mellitus. Obese subjects are twice likely to become depressed than non-obese individuals. The biological mechanisms linking depression with obesity still remain poorly understood and there is immense need...
Article
Aim: Depression and anxiety are among the most common and prevalent forms of mental disorder. The 5-hydroxytryptamine3 (5-HT 3 ) receptor antagonists modulate serotonergic pathways and show antidepressant-and anxiolytic-like effect in various animal models of depression. The present study was designed to investigate the antidepressant and anxiolyti...
Article
Background: Several preclinical studies have shown that serotonergic 5-HT3 receptor antagonists play an important role in the management of neuropsychiatric disorders, such as depression and anxiety. In the present study the compound "6n" (N-n-propyl-3-ethoxyquinoxaline-2-carboxamide), a novel 5-HT3 receptor antagonist with an optimal log P (2.52)...
Article
Full-text available
Pyridine has been used for one-pot, two-component synthesis of ethyl 3-substituted-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate derivatives in moderate to good yields by condensing N-substituted thioureas with diethyl ethoxymalonate under microwave irradiation.
Article
Despite the presence of a multitudinous pharmacotherapy, diabetes-induced depressive disorder remains undertreated. Evidence suggests that brain serotonergic deficits are associated with depressive-like behavior in diabetes and that 5HT3 receptor (5HT3R) antagonists have serotonergic facilitatory effects. This study examined the effects of a novel...
Article
Despite of the enormous research, therapeutic treatment for depression has always been a serious issue. Even though depression and obesity are individual abnormal health conditions, each act as a triggering factor for the other. Obese individuals are twice prone to develop depression than that of non-obese persons. The exact mechanism how obesity i...
Article
In our earlier study we reported the antidepressant activity of ondansetron in obese mice. The present study investigates the effect of ondansetron on depression and anxiety associated with obesity in experimental mice with biochemical evidences. Male Swiss albino mice were fed with high fat diet (HFD) for 14weeks to induce obesity. Then the subseq...
Article
In the last few decades, serotonin type-3 (5-HT3) receptor antagonists have been identified as potential targets for anxiety disorders. In preclinical studies, 5-HT3 antagonists have shown promising antianxiety effects. In this study, a novel 5-HT3 receptor antagonist, QCM-13(N-cyclohexyl-3-methoxyquinoxalin-2-carboxamide) was evaluated for anxioly...
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Full-text available
Diabetes associated depression is a largely understudied field which nonetheless carries a significant disease burden. The very low therapeutic efficacy of the existing conventional drugs with poor outcome may be, in part, due to uncertainty of the mechanism involved that clearly explains the existing comorbidity. The main purpose of this review wa...
Article
Falcipain-2 is a papain family cysteine protease and an emerging antimalarial drug target. A pseudo-tripeptide scaffold I was designed using in silico screening tools and the three dimensional structures of falcipain-2, falcipain-3, and papain. This scaffold was investigated at four positions, T1, T2, T3, and T3', with various targeted substitution...
Article
Olfactory Bulbectomy (OBX) model has been proposed as a well documented model of depression. Accumulated evidences suggest that cAMP selective PDE4 enzyme plays an important role in the pathophysiology of depression disorder. Moreover, PDE4 inhibitors have shown antidepressant-like effect in behavioral despair models. However, the potential of PDE4...
Article
Background: Malaria, an infectious disease transmitted by mosquitoes, has affected the world since the beginning of recorded human history and it remains an ensconced global health challenge even today. Among the various proteases, expressed in the life cycle of parasite, cysteine protease falcipain-2 plays a pivotal role in parasite food assimilat...
Article
Series of piperazine analogs of naphthyridine‐3‐carboxamides and indole‐2‐carboxamides were designed using a ligand‐based approach with consideration of the pharmacophoric requirements for 5‐HT3 receptor antagonists. The title carboxamides were synthesized using appropriate synthetic routes. Initially, the 5‐HT3 receptor antagonistic activity of al...
Article
Background: The cysteine protease, falcipain-2 (FP-2) is an important drug target for the management of infection by the human malaria parasite Plasmodium falciparum- The rapid emergence of resistance is the main problem with all antimalarial agents- Hence, the discovery of novel, effective drugs to counter the spread of malaria parasites that are...
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Full-text available
Aim: To investigate the antidepressant-like effects of a novel 5-HT3 receptor antagonist N-(benzo[d]thiazol-2-yl)-3-methoxyquinoxalin-2-carboxamide (6z) in acute and chronic murine models of depression. Methods: 5-HT3 receptor antagonism was examined in guinea pig ileum in vitro. A tail suspension test (TST) was used as acute depression model to e...
Article
Several preclinical studies have revealed antidepressant and anxiolytic-like effect of 5-HT3 receptor antagonists. In our earlier study, we have reported the antidepressive-like effect of 3-methoxy-N-p-tolylquinoxalin-2-carboxamide (QCM-4) in obese mice subjected to chronic stress. The present study deals with the biochemical mechanisms associated...
Article
Full-text available
The cysteine protease, falcipain-2 is an important drug target in human malaria parasite Plasmodium falciparum. A new series of 2-(4-(substituted benzoyl)-1,4-diazepan-1-yl)-N-phenylacetamide derivatives 5(a-t) were designed as per pharmacophoric requirements of falcipain-2 inhibitors using ligand-based approach. The target compounds were synthesiz...
Article
Series of piperazine analogues of naphthyridine-3-carboxamides and of indole-2-carboxamides were designed using ligand based approach with consideration of pharmacophoric requirements for the 5-HT3 receptor antagonists. The title carboxamides were synthesized using appropriate synthetic route. Initially 5-HT3 receptor antagonistic activity of all t...
Article
Increased prevalence and high comorbidity of depression-like mood disorders and diabetes have prompted investigation of new targets and potential contributing agents. There is considerable evidence supporting the inconsistent clinical efficacy and persistent undesirable effects of existing antidepressant therapy for depression associated with diabe...
Article
Background Chronic unpredictable stressors can produce a situation similar to human depression and such animal models can be used for the preclinical evaluation of antidepressants. The 5-HT3 receptor antagonists modulate serotonergic pathways and show antidepressant-like effect in various animal models of depression. Methods In this study, a novel...
Article
Anxiety disorders are widely spread psychiatric illnesses that are a cause of major concern. Despite a consistent increase in anxiolytics, the prevalence of anxiety is static; this necessitates the development of new compounds with potential activity and minimum unwanted effects. Serotonergic (5HT) system plays an important role in pathogenesis of...
Article
Rationale: Olfactory bulbectomy (OBX) is a widely used model for antidepressant screening and known to induce neurodegeneration in several brain areas. Our earlier studies demonstrated that etazolate produced antidepressant-like effects in behavioral despair models of depression; however, the potential role of etazolate on behavior and morphologic...
Article
Stimulation of high oxidative stress in brain is considered as an important factor for neurotoxicity towards the pathophysiology of chronic stress-induced depression disorder. In the present research, a potential 5-HT3 receptor antagonist N-n-butyl-3-methoxy quinoxaline-2-carboxamide (6o) having good Log P (2.60) and pA2 (7.7) values was examined f...
Article
Full-text available
Objective: 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 s...
Article
The aim of the present work was to investigate the role of ondansetron on the high fat diet (HFD) induced obese mice for behavioral and biochemical alterations using chronic unpredictable mild stress (CUMS) model of depression. Animals were fed with high fat diet for 14 weeks and subjected to different stress procedures for 4 weeks. Treatment with...
Article
Previous studies in our laboratory examined the antidepressant potential of 3-methoxy-N-p-tolylquinoxalin-2-carboxamide (QCM-4), a 5-HT3 receptor antagonist in acute and chronic rodent models of depression. The aim of present study was to investigate the effect of QCM-4 on chronic unpredictable mild stress (CUMS) induced depression in obese mice us...
Article
1,8-naphthyridine-3-carboxylic acid analogues were synthesized and found to possess potential 5-HT3 receptor antagonism as well as antidepressant like activity. Initially, 5-HT3 receptor antagonism of all the compounds was determined in the form of pA2 value against agonist 2-methyl 5-HT in longitudinal muscle myenteric plexus preparation from guin...
Article
Chronic stress is one of the major causes of depression, associated with behavioral and biochemical impairments. 5HT3 receptor antagonists (such as ondansetron) have shown alleviation of depressive symptomology in preclinical and in few clinical studies. However, their effects in chronic stress-induced depressive behavior and the underlying mechani...
Article
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 b...
Article
Full-text available
Clinical and preclinical data suggest that diabetes is often associated with anxiety. Insulin, a peptide hormone has been reported to have key functions in the brain and in alleviating several psychological impairments, occur as a consequence of diabetes. However, its effects in diabetes-induced anxiety are scanty. The present study examined whethe...
Article
Depression and anxiety are the most debilitating mood disorders with poor therapeutic recovery rates. In the last decades, 5-HT3 receptor antagonists have been identified as potential agents for mood disorders. The current investigation focuses on evaluating the, antidepressant and anti-anxiety like effects of a novel 5-HT3 antagonist, 4i (N-(3-Chl...
Article
The inconsistent therapeutic outcome necessitates designing and identifying novel therapeutic interventions for depression. Hence, the present study deals with the investigation of antidepressant-like effects of a novel 5-HT Animals were subjected to different stressors for a period of 28 days. On day 15 after the subsequent stress procedure, mice...
Article
To investigate the anti-anxiety activity of "6k", a novel 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist in in mice. Anti-anxiety activity of "6k" (1, 2, and 4 mg/kg, intraperitoneally (i.p.)) was evaluated in mice by behavioral tests such as elevated plus maze (EPM), open field test (OFT), light-dark box (L&D), and hole board test (HBT). D...
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Full-text available
The aim of the study was to evaluate a novel 5 HT3 receptor antagonist (6g) on chronic stress induced changes in behavioural and brain oxidative stress parameter in mice. A complicated relationship exists among stressful stimuli, body's reaction to stress and the onset of clinical depression. Chronic unpredictable stressors can produce a situation...
Article
Context: Increased neuronal oxidative stress as a consequence of diabetes may result in neuropsychological complications such as depression. Depression co-morbid with diabetes further hampers the quality life years in diabetic patients. Aim: Thus, the present study was aimed at investigating the effects of Adhatoda vasica leaf extract (EAV), as a n...
Article
A series of novel 1,8-naphthyridine-3-carboxamides as 5-HT3 receptor antagonists was synthesized with an intention to explore the antidepressant activity of these compounds. The title carboxamides were designed using ligand based approach keeping in consideration the structural requirement of the pharmacophore of 5-HT3 receptor antagonists. The com...
Article
The inconsistent therapeutic outcome necessitates identifying novel compounds for the treatment of depression. Therefore, the present study is aimed at evaluating the antidepressant-like effects of a novel 5-HT3 receptor antagonist 3-methoxy-N-p-tolylquinoxalin-2-carboxamide (QCM-4) on chronic unpredictable mild stress (CUMS) induced behavioral and...
Article
Depression is among the common psychiatric disorders, therefore the common pathways and pathogenesis associated with depression is required to be studied. In few years, role of 5-hydroxytryptamine-1A/B (5-HT 1A/B ) receptors in depressive disorders have been revealed. Both preclinical and clinical studies reported that the potential agonist and ant...
Article
Full-text available
The aim of this study was to investigate the anxiolytic potential of a series of novel carboxylic acid based 1,8 naphthyridines as 5-HT3 receptor antagonists. The pA2 values of all the compounds were determined against agonist 2-methyl-5-hydroxytryptamine in longitudinal muscle myenteric plexus preparations from guinea pig ileum. Compounds with hig...
Article
Preliminary study in our laboratory showed that etazolate produced antidepressant- and anxiolytic-like effects in rodent models, however, the ability of etazolate to produce antidepressant- and anxiolytic-like effects and underlying mechanism(s) in chronic unpredictable mild stress (CUMS) model have not been adequately addressed. This study was aim...
Article
The present research was designed to explore the anxiolytic-like activity of a novel 5-HT3 receptor antagonist (60) in experimental mouse models of anxiety. The anxiolytic activity of '6o' at (1 and 2 mg/kg, ip) was evaluated in mice by using a battery of behavioural tests of anxiety such as elevated plus maze (EPM), light/dark aversion test, hole...
Article
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. The compound 6p was examined in various behavioral models like forced swim test (FST), tail suspension test (TST), mechanistic models [5-hydroxytr...
Article
Depression is a neurological disorder characterized by sad mood, loss of pleasure, agitation and retardation. Though most relevant neuronal pathophysiology is characterized by decrease in monoamine namely; serotonin (5-HT), dopamine, noradrenaline level in central areas regulating mood and behavior, it inadequately explains the exact mechanism invo...
Article
The present research was designed to explore the anxiolytic-like activity of a novel 5-HT3 receptor antagonist (6o) in experimental mouse models of anxiety. The anxiolytic activity of '6o' at (1 and 2 mg/kg, ip) was evaluated in mice by using a battery of behavioural tests of anxiety such as elevated plus maze (EPM), light/dark aversion test, hole...
Article
The compound 6o (at 0.5, 1 and 2 mg/kg, ip) with optimum log P and pA2 value, was subjected to forced swim test (FST) and tail suspension test (TST). The compound 6o significantly reduced the duration of immobility in mice without affecting the base line locomotion in actophotometer. Moreover, 6o (2 mg/kg, ip), potentiated the 5-hydroxytryptophan (...
Article
Etazolate is a selective inhibitor of type 4 phosphodiesterase (PDE4) class enzyme. Antidepressant-like effect of etazolate has been previously demonstrated in the rodent models of depression. The present study was designed to investigate the anxiolytic-like activity of etazolate in experimental mouse models of anxiety. The putative anxiolytic effe...
Article
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 behavioral tests battery of depression. Acute treatment of 7a (0.5-2mg/kg, i.p.) in m...
Article
The present study was designed to investigate the anxiolytic activity of 6g, a novel serotonin type-3 receptor (5-HT3) receptor antagonist in experimental mouse models of anxiety. The anxiolytic activity of "6g" (1 and 2 mg/kg, intraperitoneally [i.p.]) was evaluated in mice by using a battery of behavioral tests of anxiety such as elevated plus ma...
Article
Full-text available
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...
Article
Etazolate, a pyrazolopyridine class compound is selective inhibitor of type 4 phosphodiesterase (PDE4). Previous study in our laboratory has demonstrated that etazolate produced antidepressant-like effect in rodent models of behavioral despair. The present study was designed to investigate whether etazolate could affect the chronic unpredictable mi...
Article
Employing a ligand-based approach, 3-methoxyquinoxalin-2-carboxamides were designed as serotonin type-3 (5-HT(3) ) receptor antagonists and synthesized from the starting material o-phenylenediamine in a sequence of reactions. The structures of the synthesized compounds were confirmed by spectral data. These carboxamides were investigated for their...
Article
Full-text available
The present study was designed to evaluate the antidepressant potential of 5-HT3 receptor antagonist N-n-propyl-3-ethoxyquinoxaline-2-carboxamide (6n). The compound '6n' with optimum log P and pA 2 value identified from a series of compounds synthesized in our laboratory was subjected to forced Swim Test (FST) (1, 2, and 4 mg/kg, i.p) and Tail Susp...
Article
Linezolid, an oxazolidinone class antibiotic is a reversible and nonselective inhibitor of monoamine oxidase (MAO) enzyme, mainly for MAO-A subtype. Its antidepressant-like effect has been previously demonstrated in the rodent models of depression. MAO-A enzyme has been shown to play a role in the pathophysiology of anxiety disorders and inhibition...
Article
Full-text available
The present study was designed to investigate the antidepressant potential of (4-phenylpiperazin-1-yl) (quinoxalin-3-yl) methanone (4a), a novel 5-HT(3) receptor antagonist, with an optimal log P (2.84) and pA(2) value (7.3) greater than ondansetron (6.9) using rodent behavioural models of depression. Swiss albino mice were used in actophotometer t...