Browsing by Author "Mahesh, R."

Now showing 1 - 20 of 112

1-(m-Chlorophenyl)piperazine induces depressogenic-like behaviour in rodents by stimulating the neuronal 5-HT2A receptors: Proposal of a modified rodent antidepressant assay
(Elsevier, 2009-04) Mahesh, R.
1-(m-Chlorophenyl)piperazine (mCPP) has a fairly complex neuropsychopharmacological profile owing to its affinity to multiple serotonergic receptors. This investigation was designed to establish the effect of mCPP on rodent depression-like behaviour. mCPP was screened in a rodent behavioural test battery comprising of validated antidepressant assays and interaction studies with conventional antidepressants and ligands were carried out in forced swim and tail suspension test (in mice). mCPP (1 mg/kg, i.p.) exhibited depressant-like effects in forced swim and tail suspension test (in mice), without influencing the locomotor status. Potentiation of 5-hydroxytryptophan/pargyline induced head twitches (in mice) and hyperthermic effects (in rats) were observed at the same dose level. Further, the behavioural anomalies of the olfactory bulbectomised (OBX) rats were augmented by chronic mCPP (1–2 mg/kg) treatment as observed from the modified open field, elevated plus maze and social interaction paradigms. Interaction studies revealed that the mCPP induced depressant-like effects were reversed by ketanserin, escitalopram, amitriptyline, ziprasidone, venlafaxine pretreatments but not by bupropion, harmane, ondansetron, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and MK-801. In conclusion, this study provided ample evidence that the stimulation of 5-HT2A receptors underlies the depressogenic-like effect of mCPP. Finally, the mCPP induced depression-like behaviour in rodents is envisaged as a modified antidepressant assay to identify novel serotonergic antidepressants.
2-(4-substituted piperazin-1-yl)-1,8-naphthyridine-3-carboxylic acids: Novel 5-HT3 receptor antagonists with anxiolytic-like activity in rodent behavioral models
(Candian Journal, 2013-06) Mahesh, R.
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 higher pA2 values, particularly those greater than ondansetron, a standard 5-HT3 receptor antagonist, and optimal log P values were screened in mice by using behavioral tests such as a light–dark (L/D) aversion test, elevated plus maze (EPM) test, and an open field test (OFT). In the L/D test, compounds 7a, 7b, 7d, 7e, and 7i (2 mg/kg body mass, intraperitoneal) significantly (P < 0.05) increased the latency time to leave the light compartment, total time spent in the light compartment, and the number of transitions between the light and dark compartments. Compounds 7a, 7d, 7f, 7h, and 7i (2 mg/kg, i.p.) significantly (P < 0.05) increased the time spent in the open arms and the number of entries into the open arms in the EPM test. In addition, compounds 7a, 7d, 7e, 7f, and 7h (2 mg/kg, i.p.) significantly (P < 0.05) increased the ambulation scores and the frequency of rearing in the OFT.
2-(4-substituted piperazin-1-yl)-1,8-naphthyridine-3-carboxylic acids: Novel 5-HT3 receptor antagonists with anxiolytic-like activity in rodent behavioral models
(CSP, 2013-06) Mahesh, R.
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 higher pA2 values, particularly those greater than ondansetron, a standard 5-HT3 receptor antagonist, and optimal log P values were screened in mice by using behavioral tests such as a light–dark (L/D) aversion test, elevated plus maze (EPM) test, and an open field test (OFT). In the L/D test, compounds 7a, 7b, 7d, 7e, and 7i (2 mg/kg body mass, intraperitoneal) significantly (P < 0.05) increased the latency time to leave the light compartment, total time spent in the light compartment, and the number of transitions between the light and dark compartments. Compounds 7a, 7d, 7f, 7h, and 7i (2 mg/kg, i.p.) significantly (P < 0.05) increased the time spent in the open arms and the number of entries into the open arms in the EPM test. In addition, compounds 7a, 7d, 7e, 7f, and 7h (2 mg/kg, i.p.) significantly (P < 0.05) increased the ambulation scores and the frequency of rearing in the OFT.
4i (N-(3-Chloro-2-methylphenyl) quinoxalin-2-carboxamide), a novel 5-HT3 receptor antagonist alleviates depressive behavior evoked in streptozotocin-induced diabetic mice: Role of oxidative stress
(Elsevier, 2016-01) Mahesh, R.
The prevalence of depression is about 2-3 times higher in diabetic patients compared to the general population, yet this comorbidity is poorly treated. This may partly be contributed to the inefficient pharmacotherapy. We evaluated if a novel 5HT3 receptor antagonist 4i (N-(3-Chloro-2-methylphenyl) quinoxalin-2-carboxamide), can prevent depression-like behavior associated with diabetes in mice. Also, the role of oxidative stress in antidepressant action of 4i was investigated.
5HT3 receptor antagonist (ondansetron) reverses depressive behavior evoked by chronic unpredictable stress in mice: Modulation of hypothalamic–pituitary–adrenocortical and brain serotonergic system
(Elsevier, 2014-09) Mahesh, R.
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 mechanism(s) are yet to be known. In the present study, the effects of a 5HT3 receptor antagonist, ondansetron were evaluated in chronic unpredictable stress (CUS)-evoked depressive behavior. In addition, the possible mechanism was determined by measuring plasma corticosterone (CORT) as a marker of hypothalamic–pituitary–adrenocortical (HPA)-axis activity and serotonin levels in the discrete brain regions. Mice were subjected to a battery of unpredictable stressors for 28 days. Ondansetron (0.05, 0.1 and 1 mg/kg, p.o.) and fluoxetine (10 mg/kg, p.o.) were administered during the last 14 days (day 15–28th) of CUS testing paradigm. The results showed that the 4-week CUS produced significant depressive behavior in mice, which included increased despair effects in forced swim test (FST) and reward-related deficits in sucrose preference test. Biochemical assays demonstrated a significant increase in percentage of plasma CORT and decrease in percentage of serotonin levels in the discrete brain regions of CUS mice. Chronic ondansetron treatment, similar to that of positive control fluoxetine, significantly reversed despair effects in FST and reward-related deficits in sucrose preference test. In addition, ondansetron and fluoxetine treatments significantly increased percentage of serotonin levels in the measured brain regions and attenuated HPA-axis hyperactivity, as evidenced by low percentage of plasma CORT levels in CUS mice. These findings indicate the potential role of ondansetron (a 5HT3 receptor antagonist) in reversing CUS-induced depressive behavior, which is possibly mediated by its modulating effects on the HPA-axis and serotonergic system. Further, the study represents that 5HT3 receptor antagonists can be a potential therapeutic candidate for stress-related depressive disorders.
5HT3 receptors: Target for new antidepressant drugs
(Elsevier, 2016-05) Mahesh, R.
5HT3 receptors (5HT3Rs) have long been identified as a potential target for antidepressants. Several studies have reported that antagonism of 5HT3Rs produces antidepressant-like effects. However, the exact role of 5HT3Rs and the mode of antidepressant action of 5HT3R antagonists still remain a mystery. Here, we provide a comprehensive overview of 5HT3Rs: (a) regional and subcellular distribution of 5HT3Rs in discrete brain regions, (b) preclinical and clinical evidence supporting the antidepressant effect of 5HT3R antagonists, and (c) neurochemical, biological and neurocellular signaling pathways associated with the antidepressant action of 5HT3R antagonists. 5HT3Rs located on the serotonergic and other neurotransmitter interneuronal projections control their release and affect mood and emotional behavior; however, new evidence suggests that apart from modulating the neurotransmitter functions, 5HT3R antagonists have protective effects in the pathogenic events including hypothalamic–pituitary–adrenal-axis hyperactivity, brain oxidative stress and impaired neuronal plasticity, pointing to hereby unknown and novel mechanisms of their antidepressant action. Nonetheless, further investigations are warranted to establish the exact role of 5HT3Rs in depression and antidepressant action of 5HT3R antagonists.
Ameliorative Effect of Wortmannin and Rapamycin Treatment on Obesity Markers in High Fat Diet Feed Rats
(IJPER, 2015-02) Mahesh, R.
Obesity is a metabolic disorder, characterized by a chronic excess of energy intake over expenditure, leading to the accumulation of that excess as fat. Obesity is associated with adipocyte hypertrophy and adipocyte hyperplasia. PI3K and mTOR, both key signaling molecules critically regulating the adipogenesis and adipocyte differentiation. Thus, the present study investigates the efficacy of wortmannin, a PI3K inhibitor and rapamycin, a mTOR inhibitor on the anthropometrical parameters (body weight, Body Mass Index, Lee index, feed intake), and fat depots in High Fat Diet (HFD)-Induced obesity. The obesity in rats was produced by feeding HFD for a period of 8 weeks. The study explored the effect of wortmannin (100μg/kg/day i.p) and rapamycin (0.75mg/kg/day i.p) on abnormal anthropometrical parameters, fat pads weight and liver weight/ body weight ratio (%) resulted from HFD in rats. The present study findings indicated that treatment with wortmannin and rapamycin significantly (p<0.05) reversed the abnormal effect of HFD on anthropometrical parameters, different fat pads weight and liver weight/ body weight ratio (%) as compared to Normal diet. Therefore Wortmannin & Rapamycin may serve as the potential candidates for the treatment of obesity.
Anti-anxiety effect of a novel 5-HT3 receptor antagonist N-(benzo[d]thiazol-2-yl)-3-ethoxyquinoxalin-2-carboxamide (6k) using battery tests for anxiety in mice
(Wolters Kluwer, 2014) Mahesh, R.
To investigate the anti-anxiety activity of “6k”, a novel 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist in in mice.
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.
Anti-depressant like activity of N-n-butyl-3-methoxyquinoxaline-2-carboxamide (6o) a 5-HT3 receptor antagonist
(NISCAIR, 2013-06) Mahesh, R.
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 (5-HTP)-induced head twitch responses in mice and at 1 and 2 mg/kg, ip antagonized the reserpine-induced hypothermia (RIH) in rats. In interaction studies with various standard drugs/ligands using FST, 6o (1 and 2 mg/kg, ip) potentiated the anti-depressant effect fluoxetine (5 mg/kg, ip) and reversed the depressant effect of parthenolide (1 mg/kg, ip) by reducing the duration of immobility. Furthermore, 6o (1 and 2 mg/kg, ip) potentiated the effect of bupropion (10 mg/kg, ip) in TST. The behavioural anomalies of the olfactory bulbectomised (OBX) rats were augmented by chronic 6o (1 and 2 mg/kg) treatment as observed from the modified open field test (parameters: ambulation, rearing, fecal pellet). The results suggest that compound 6o exhibited anti-depressant like effect in rodent models of depression.
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.
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.
Anti-depressant-like activity of a novel serotonin type-3 (5-HT3) receptor antagonist in rodent models of depression
(NISCAIR, 2011) Mahesh, R.
N-Cyclohexyl-3-methoxyquinoxalin-2-carboxamide (QCM-13), a novel 5-HT3 antagonist identified from a series of compounds with higher pA2 (7.6) and good log P (2.91) value was screened in rodent models of depression such as forced swim test (FST), tail suspension test (TST), interaction studies with standard anti-depressants and confirmatory studies such as reversal of parthenolide induced depression and reserpine induced hypothermia. In FST (2 and 4 mg/kg) and TST (2 and 4 mg/kg), QCM-13 significantly reduced the duration of immobility in mice without affecting the base line locomotion. QCM-13 (2 and 4 mg/kg) was also found to have significant interaction with standard anti-depressants (fluoxetine and bupropion in FST and TST respectively). Further, reversal of parthenolide induced depression in mice and reserpine induced hypothermia in rat models indicate the serotonergic influence of QCM-13 for anti-depressant potential.
Anti-Depressant-Like Activity of Mucuna Pruriens; A Traditional Indian Herb in Rodent Models of Depression
(2010-01) Mahesh, R.; Jhadav, Hemant R.
The anti-depressant-like effects of Mucuna pruriens (MP) were studied in validated models of depression. Psycho-pharmacological investigations involved acute and chronic treatment (14 days) of mucuna 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 anti-depressant-like effect of Mucuna (10-20 mg/kg i.p.). Interaction studies revealed that, mucuna (10 mg/kg) significantly enhanced the anti-depressant action of fluoxetine and bupropion in FST and TST respectively. Potentiation of 5-Hydroxytryptophan induced head twitches response (in mice) and reversal of reserpine induced hypothermia (rats) were observed at same dose level. Further, the behaviour anomalies exhibited by olfactory bulbectomised rats (OBX) were attenuated by chronic mucuna treatment as observed in open field. In conclusion, this behavioural study depicts the anti-depressant-like effect of mucuna in acute and chronic model of depression.
Antidepressant & anxiolytic activities of N-(pyridin-3-yl) quinoxalin-2-carboxamide: A novel serotonin type 3 receptor antagonist in behavioural animal models
(IJMR, 2016) Mahesh, R.
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-carboxamide (QCF-21), a novel 5-HT3 receptor antagonist in preclinical models of depression and anxiety.
Antidepressant and anti-anxiety like effects of 4i (N-(3-chloro-2-methylphenyl) quinoxalin-2-carboxamide), a novel 5-HT3 receptor antagonist in acute and chronic neurobehavioral rodent models
(Elsevier, 2014-07) Mahesh, R.
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-chloro-2-methylphenyl) quinoxalin-2-carboxamide). Preliminary, in vitro 5-HT3 receptor binding affinity was performed in isolated longitudinal muscle-myenteric plexus from the guinea pig ileum. Consequently, neurobehavioral effects of 4i in acute and chronic rodent models were evaluated. In addition, involvement of serotonergic system in the postulated effects of the compound was analyzed by in vivo assay. in vitro, 4i demonstrated high 5-HT3 receptor antagonistic activity (pA2, 7.6). in vivo acute study, 4i exhibited decreased duration of immobility in forced swim and tail suspension tests, and increased exploratory parameters as number and duration of nose-poking in hole board test and latency and time spent in aversive brightly illuminated light chamber in light–dark model. Moreover, in chronic model of depression, i.e., olfactory bulbectomy with behavioral deficits, 4i reversed depressive anhedonia in sucrose preference test and anxious hyperactive behavior in open field test in rats. Furthermore, synergistic effect of 4i with fluoxetine (a selective serotonin reuptake inhibitor) and inhibitory effect of 1-(m-chlorophenyl)-biguanide (a 5-HT3 receptor agonist) revealed serotonergic modulation by 4i mediated 5-HT3 receptor antagonism, which was further confirmed by potentiation of 5-hydroxytryptophan (a serotonin synthesis precursor) induced head twitch response. These findings suggest the potential antidepressant and anti-anxiety like effects of 4i, which may be related to the modulation of serotonergic system.
Antidepressant effects of insulin in streptozotocin induced diabetic mice: Modulation of brain serotonin system
(Elsevier, 2014-04) Mahesh, R.
Diabetes is a persistent metabolic disorder, which often leads to depression as a result of the impaired neurotransmitter function. Insulin is believed to have antidepressant effects in depression associated with diabetes; however, the mechanism underlying the postulated effect is poorly understood. In the present study, it is hypothesized that insulin mediates an antidepressant effect in streptozotocin (STZ) induced diabetes in mice through modulation of the serotonin system in the brain. Therefore, the current study investigated the antidepressant effect of insulin in STZ induced diabetes in mice and insulin mediated modulation in the brain serotonin system. In addition, the possible pathways that lead to altered serotonin levels as a result of insulin administration were examined. Experimentally, Swiss albino mice of either sex were rendered diabetic by a single intraperitoneal (i.p.) injection of STZ. After one week, diabetic mice received a single dose of either insulin or saline or escitalopram for 14 days. Thereafter, behavioral studies were conducted to test the behavioral despair effects using forced swim test (FST) and tail suspension test (TST), followed by biochemical estimations of serotonin concentrations and monoamine oxidase (MAO) activity in the whole brain content. The results demonstrated that, STZ treated diabetic mice exhibited an increased duration of immobility in FST and TST as compared to non-diabetic mice, while insulin treatment significantly reversed the effect. Biochemical assays revealed that administration of insulin attenuated STZ treated diabetes induced neurochemical alterations as indicated by elevated serotonin levels and decreased MAO-A and MAO-B activities in the brain. Collectively, the data indicate that insulin exhibits antidepressant effects in depression associated with STZ induced diabetes in mice through the elevation of the brain serotonin levels.
Antidepressant Potential of 5-HT3 Receptor Antagonist, N-n- propyl-3-ethoxyquinoxaline-2-carboxamide (6n)
(Elsevier, 2012-12) Mahesh, R.
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 pA2 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 Suspension Test (TST) (1, 2, and 4 mg/kg, i.p.). The Compound '6n' significantly reduced the duration of immobility in mice without affecting the baseline locomotion. Moreover, '6n' (2 mg/kg, i.p.) potentiated the 5-hydroxytryptophan (5-HTP)-induced head twitch responses in mice and '6n' attested dose (1 and 2 mg/kg, i.p.) reversed the reserpine-induced hypothermia in rats. In interaction studies of '6n' with various Standard drugs/ligands using FST, '6n' (1 mg/kg, i.p.) potentiated the antidepressant effect of venlafaxine (4 and 8 mg/kg, i.p.) and fluoxetine (10 and 20 mg/kg, i.p.). Additionally, '6n' (1 and 2 mg/kg, i.p.) influenced the effect of harmane (5 mg/kg, i.p.) as well as reversed the effect of parthenolide (1 mg/kg, i.p.) by reducing the duration of immobility in FST. Furthermore, '6n' (1 mg/kg, i.p.) potentiated the effect of bupropion (10 and 20 mg/kg, i.p.) in TST. Chronic '6n' (1 and 2 mg/kg, i.p.) treatment attenuated the behavioral abnormalities in olfactory bulbectomized rats. In conclusion, these various findings reiterated the antidepressant-like effects of'6n' in behavioral models of depression.
Antidepressant Therapy for Depression: An Update
(Springer, 2017-10) Mahesh, R.
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 correction of monoamine deficit. However, over time, many different strategies have been determined in an effort to improve the efficacy and reduce the untoward effects of the therapeutic intervention. This chapter compiles the relative efficacy and plausible mechanism of antidepressant activity of most current therapeutic approaches targeting a wide range of molecular and cellular pathways, implicated in the pathogenesis of depression. Emerging knowledge of key pathogenic mechanisms, such as the impairment of non-monoaminergic neurotransmission, in addition to monoaminergic neurotransmission, hypothalamic-pituitary-adrenal axis hyperactivity, alteration in neurogenesis signaling pathways, enhanced brain oxidative stress, and inflammatory activity, has led to a host of new molecular drug targets. Several of these have been validated through the preliminary use of lead compounds and therapeutic agents in animals and humans
Antidepressant- and anxiolytic-like effect of novel 5-hydroxytryptamine3 receptor antagonist 2-[4-(3-chlorophenyl) piperazin-1-yl]-1,8-naphthyridine -3-carboxylic acid (7e)- An approach using rodent behavioral antidepressant and anxiolytic test battery
(Wolters Kluwer, 2016-06) Mahesh, R.
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 anxiolytic potential of 2-[4-(3-chlorophenyl) piperazin-1-yl]- 1,8-naphthyridine-3-carboxylic acid (7e), a novel 5-HT 3 receptor antagonist in rodent behavioral models of depression and anxiety.