Protective effect of Thiocolchicoside against Haloperidol Induced Orofacial Dyskinesia and Catalepsy in Rats
Dipti D. Pore*, Atish B. Velhal, Vivekkumar K. Redasani
Department of Pharmacology, YSPM’s Yashoda Technical Campus, Satara, Maharashtra, India.
*Corresponding Author E-mail: diptipore1999@gmail.com
ABSTRACT:
The goal of the current study was to assess thiocolchicoside's impact on catalepsy and orofacial dyskinesia in wistar male albino rats that had been induced by haloperidol. The neurodegenerative illness known as catalepsy, whose cause is unclear, is typified by motor symptoms such as bradykinesia, tremor, rigidity in the muscles, and instability in one's posture. It's a disorder marked by a tendency to remain motionless, a decrease in reactivity to stimuli and inactivity. The inability to adjust one's posture in response to external signals is known as catalepsy. Tardive dyskinesia is an iatrogenic illness defined by late-onset hyperkinetic involuntary dyskinesia, usually affecting the orofacial region, caused by long-term use of classical neuroleptics. Neuroleptics causes blockade of dopaminergic (DA) transmission produces catalepsy. Haloperidol blocks dopamine D2 receptors and reduces dopaminergic transmission in the basal ganglia, which puts animals in a state of catalepsy. The anticataleptic study was carried out on animal model such as haloperidol induced orofacial dyskinesia and catalepsy. Animals of this model were treated with std. drug levodopa/carbidopa (125mg/kg) and test drug thiocolchicoside low dose (4mg/kg), high dose (8mg/kg). The persistent injection of haloperidol to rats resulted in a considerable increase in catalepsy, tongue protrusions, and vacuous chewing motions (VCMs). These results indicate that thiocolchicoside possess anticataleptic effect against haloperidol induced catalepsy in rats. The results indicated strong anticataleptic efficacy, suggesting that thiocolchicoside may be useful in the treatment of catalepsy.
The components AADC and VMAT 2 that are required for serotonergic neurons to convert L-DOPA into dopamine are present1.
Dopaminergic medications can be used to treat its motor symptoms, but as the underlying neurodegeneration progresses and the severity of clinical symptoms increases, they become less effective. Tardive dyskinesia is an iatrogenic illness defined by late-onset hyperkinetic involuntary dyskinesia, usually affecting the orofacial region, caused by long-term use of classical neuroleptics. Dopamine hypersensitivity and elevated oxidative stress may be the cause of tardive dyskinesia2.
In the rat central nervous system, thiocolchicoside (THC) has been shown to interact with g-amino butyric acid (GABA) type A receptors (GABAARs) and strychnine-sensitive glycine receptors. Because of its analgesic, muscle relaxant, and anti-inflammatory properties, thiocolchicoside is used in medical treatments. Because of its strong and specific affinity for GABA-A receptors, thiocolchicoside functions as a powerful muscle relaxant by causing the GABA inhibitory pathways to be activated, which in turn relieves muscular contractures. It also functions as a muscle relaxant because of its affinity for the inhibitory glycine receptors, which enables it to have glycomimetic and GABA mimetic effects3.
Haloperidol lowers dopamine neurotransmission and prevents the hallucinations and delusions that are frequently connected to psychosis by specifically blocking post-synaptic dopamine (D2) receptors in the brain. It primarily acts on D2-receptors, having very little effect on dopamine D1 receptors and just slight effects on α-1 and 5-HT2 receptors. For the majority of parkinsonian patients, replacement therapy using the dopamine precursor L-dihydroxyphenylalanine (L-dopa) is effective. In modern practice, carbidopa or benserazide, a peripheral decarboxylase inhibitor, is always given with L-dopa to prevent peripheral decarboxylation and allows maximum amount of levodopa to reach the CNS4.
MATERIALS AND METHODS:
Experimental Animals:
The experiment was conducted on 30 male wistar albino rats weighing between 150-200gm obtained from animal house, YSPM’s Yashoda Technical campus, Satara. The current study does not include female rats because it has been shown that estrogen has neuroprotective properties this might mask the development of catalepsy.
Housing of animals:
Paddy husks served as bedding in the polypropylene cages that held the animals. The animals were kept under typical laboratory environments, which included a temperature of 22±2℃, a relative humidity of 50±15%, a light and dark cycle of 12 hours each, and free access to water and pellet food. The experiment was carried out in accordance with the policies set forth by the Indian government's Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA). The Institutional Animal Ethics Committee gave its approval to the study protocol (IAEC).
Experimental design:
In this study, thirty albino rats were employed. Five groups of male albino rats weighing between 150 and 200 grams each were created at random. For each group, there were six animals used as the study's model.
Group I (n=6): Vehicle
Group II (n=6): Haloperidol (1mg/kg, i.p)
Group III(n=6): Haloperidol (1mg/kg, i.p) + Levodopa/ Carbidopa (125mg/kg, p.o)
Group IV (n=6): Thiocolchicoside (4mg/kg,p.o) + Haloperidol (1mg/kg, i.p)
Group V (n=6): Thiocolchicoside (8mg/kg, p.o) + Haloperidol (1mg/kg, i.p)
Chemicals and Drugs:
Haloperidol (Serenace®, RPG Life Sciences Ltd., Gujarat, India), thiocolchicoside (Myoril®, CORONA Remedies Private Limited, Gujarat, India), Levodopa and Carbidopa (SYNDOPA® plus, Sun pharma laboratories Ltd., Gangtok, Sikkim) were employed in the research. The study exclusively employed analytical grade reagents for all other reagents. The literature was used to determine the drug doses, which were as follows: 1mg/kg for haloperidol2 and 4 and 8mg/kg for thiocolchicoside3.
Experimental Procedure:
Haloperidol Induced Catalepsy (HIC):
Haloperidol (1mg/kg body weight) was injected intraperitoneally thirty minutes after the vehicle/drugs were provided in order to cause orofacial dyskinesia and catalepsy over the course of 21 consecutive days. In order to determine attenuation or potentiation of the phenomena, a moderate degree of catalepsy was induced by this dose of haloperidol2. Following the delivery of haloperidol, the degree of catalepsy was measured using a technique identical to the conventional bar test at 30, 60, 120, 180, and 240 minutes. A high bar test method was used to quantify a cataleptic's behaviour. After administering haloperidol for four hours, the catalepsy score was determined every hour. In this test, the rat's front paws were gently positioned 6cm above the tabletop on a horizontal metal bar with a diameter of 2 to 5mm. The duration in seconds that the rat took to remove both of its forepaws down to the tabletop was used to assessed the severity of catalepsy5,6. The test was stopped when the paws of the animal touches the tabletop or the cut-off time of 180 seconds pass. The animal receives a score of 0 seconds if the animals do not hold on the bar after the three attempts4.
Scoring of catalepsy:
The length of time a cataleptic animal stays in this posture depends on the severity of its catalepsy. The animal received one point and was labelled as cataleptic if the animal held the forced position for a minimum of twenty seconds. The scoring system has been adjusted from Costall and Naylor's (1974) original. In order to receive a score, an animal must maintain the cataleptic posture for the following durations: 0 to 10 seconds scored 0; 10 to 30 seconds= 1; 30 seconds to 1min= 2; 1 min to 2min=3; 2min to 3 min= 4; 3min to ∞=5. After receiving haloperidol medication, the animals were examined for catalepsy at 0.5, 1.0, 2.0, 3.0, and 4.0 hours7.
Statistical Analysis:
All the results were expressed as mean±SEM. The data obtained by the various parameters was statistically evaluated by one way analysis of variance (ANOVA) followed by Dunnetts ‘t’ test using graph pad instant 10. The level of significance was set at p<0.05.
RESULT:
Effect of Thiocolchicoside on catalepsy score by using High bar test:
Table 1. Effect of Thiocolchicoside on catalepsy score (Day 7)
|
Groups |
Treatment (Dose) |
30 min |
60 min |
120 min |
180 min |
240 min |
|
Group I (Normal Control) |
Vehicle (10 ml/kg) |
0.00±0.00 |
0.00±0.00 |
0.00±0.00 |
0.00±0.00 |
0.00±0.00 |
|
Group II (Negative Control) |
Haloperidol (1mg/kg) |
1.65±0.13 |
1.68±0.14 |
1.70±0.14 |
1.72±0.15 |
1.73±0.15 |
|
Group III (Positive Control) |
Haloperidol (1mg/kg) + Levodopa/Carbidopa (125mg/kg) |
1.36±0.11 |
1.33±0.10 |
1.30±0.10 |
1.28±0.09 |
1.25±0.09 |
|
Group IV (Test-1) (Low Dose) |
Thiocolchicoside (4mg/kg) + Haloperidol (1 mg/kg) |
1.42±0.12 |
1.39±0.11 |
1.37±0.11 |
1.35±0.11 |
1.32±0.10 |
|
Group V (Test-2) (High Dose) |
Thiocolchicoside (8mg/kg) + Haloperidol (1 mg/kg) |
1.55±0.13 |
1.52±0.13 |
1.49±0.12 |
1.46±0.12 |
1.43±0.11 |
All values are expressed as mean ± SEM; n=6 rats in each group, data was analysed by one way ANOVA followed by Dunnetts ‘t’ test. *p<0.05, **p<0.01, ***p<0.001.
Table 2. Effect of Thiocolchicoside on catalepsy score (Day 14)
|
Groups |
Treatment (Dose) |
30 min |
60 min |
120 min |
180 min |
240 min |
|
Group I (Normal Control) |
Vehicle (10 ml/kg) |
0.00±0.00 |
0.00±0.00 |
0.00±0.00 |
0.00±0.00 |
0.00±0.00 |
|
Group II (Negative Control) |
Haloperidol (1 mg/kg) |
1.62±0.13 |
1.76±0.14 |
1.83±0.16 |
2.00±0.17 |
1.94±0.17 |
|
Group III (Positive Control) |
Haloperidol (1 mg/kg) + Levodopa/Carbidopa (125mg/kg) |
0.00±0.00 |
0.00±0.00 |
0.00±0.00 |
0.00±0.00 |
0.00±0.000 |
|
Group IV (Test-1) (Low Dose) |
Thiocolchicoside (4mg/kg) + Haloperidol (1 mg/kg) |
0.00±0.00 |
0.00±0.00 |
0.00±0.00 |
0.72±0.05 |
0.69±0.04 |
|
Group V (Test-2) (High Dose) |
Thiocolchicoside (8mg/kg) + Haloperidol (1 mg/kg) |
0.00±0.00 |
0.89±0.06 |
0.86±0.06 |
0.84±0.05 |
0.81±0.05 |
All values are expressed as mean ± SEM; n=6 rats in each group, data was analysed by one way ANOVA followed by Dunnetts ‘t’ test. *p<0.05, **p<0.01, ***p<0.001.
In table-1, the effect of thiocolchicoside has significantly affected the cataleptic score. The Negative Control (Group-II) Haloperidol (1mg/kg i.p.) showed significant elevation in the cataleptic score as compared to Normal Control (Group-I) animals. Group-III treated by Levodopa/Carbidopa (125mg/kg p.o.) showed significant reduction in cataleptic score at 7th day as compared to Negative Control (Group-II). Test 1 (Group-IV) treated by low dose of thiocolchicoside (4mg/kg p.o) showed significant reduction in the cataleptic score at 7th day as compared to Negative Control (Group-II). Test 2 (Group-V) treated by high dose of thiocolchicoside (8mg/kg p.o) showed significant reduction in the cataleptic score at 7th day as compared to Negative Control (Group-II).
In table-2, the effect of thiocolchicoside has significantly affect the cataleptic score. The Negative Control (Group-II) Haloperidol (1mg/kg i.p.) showed significant elevation in the cataleptic score as compared to Normal Control (Group-I) animals. Group-III treated by Levodopa/Carbidopa (125mg/kg p.o.) showed more significant reduction in cataleptic score at 14th day as compared to Negative Control (Group-II). Test 1 (Group-IV) treated by low dose of thiocolchicoside (4mg/kg p.o) showed significant reduction in the cataleptic score at 14th day as compared to Negative Control (Group-II). Test 2 (Group-V) treated by high dose of thiocolchicoside (8mg/kg p.o) showed significant reduction in the cataleptic score at 14th day as compared to Negative Control (Group-II).
Table 3. Effect of Thiocolchicoside on catalepsy score (Day 21)
|
Groups |
Treatment (Dose) |
30 min |
60 min |
120 min |
180 min |
240 min |
|
Group I (Normal Control) |
Vehicle (10ml/kg) |
0.00±0.00 |
0.00±0.00 |
0.00±0.00 |
0.00±0.00 |
0.00±0.00 |
|
Group II (Negative Control) |
Haloperidol (1mg/kg) |
2.50±0.22 |
2.58±0.22 |
2.64±0.23 |
2.60±0.23 |
2.82±0.25 |
|
Group III (Positive Control) |
Haloperidol (1mg/kg) + Levodopa/Carbidopa (125mg/kg) |
0.00±0.00 |
0.00±0.00 |
0.00±0.00 |
0.00±0.00 |
0.00±0.00 |
|
Group IV (Test-1) (Low Dose) |
Thiocolchicoside (4mg/kg) + Haloperidol (1mg/kg) |
0.00±0.00 |
0.00±0.00 |
0.00±0.00 |
0.00±0.00 |
0.00±0.00 |
|
Group V (Test-2) (High Dose) |
Thiocolchicoside (8mg/kg) + Haloperidol (1mg/kg) |
0.00±0.00 |
0.00±0.00 |
0.67±0.04 |
0.62±0.04 |
0.59±0.03 |
All values are expressed as mean ± SEM; n=6 rats in each group, data was analysed by one way ANOVA followed by Dunnetts ‘t’ test. *p<0.05, **p<0.01, ***p<0.001.
In table-3, the effect of thiocolchicoside has significantly affect the cataleptic score. The Negative Control (Group-II) Haloperidol (1mg/kg i.p.) showed significant elevation in the cataleptic score as compared to Normal Control (Group-I) animals. Group-III treated by Levodopa/Carbidopa (125mg/kg p.o.) showed more significant reduction in cataleptic score at 21st day as compared to Negative Control (Group-II). Test 1 (Group-IV) treated by low dose of thiocolchicoside (4mg/kg p.o) showed more significant reduction in the cataleptic score at 21st day as compared to Negative Control (Group-II). Test 2 (Group-V) treated by high dose of thiocolchicoside (8mg/kg p.o) showed significant reduction in the cataleptic score at 21st day as compared to Negative Control (Group-II).
Effect of Thiocolchicoside on locomotor activity by using Actophotometer:
Table 4. Effect of Thiocolchicoside on locomotor activity (Day 7)
|
Groups |
Treatment (Dose) |
Number of Locomotor activity in 10 min |
|
Group I (Normal Control) |
Vehicle (10 ml/kg) |
386±36.2 |
|
Group II (Negative Control) |
Haloperidol (1 mg/kg) |
194±17.6 |
|
Group III (Positive Control) |
Haloperidol (1mg/kg) + Levodopa/Carbidopa (125mg/kg) |
291±27.2 |
|
Group IV (Test-1) (Low Dose) |
Thiocolchicoside (4mg/kg) + Haloperidol (1 mg/kg) |
279±25.3 |
|
Group V (Test-2) (High Dose) |
Thiocolchicoside (8mg/kg) + Haloperidol (1 mg/kg) |
263±23.9 |
All values are expressed as mean ± SEM; n=6 rats in each group, data was analysed by one way ANOVA followed by Dunnetts ‘t’ test. *p<0.05, **p<0.01, ***p<0.001.
In table-4, the Negative Control (Group-II) Haloperidol (1mg/kg i.p.) administration showed significant reduction in the locomotor activity as compared to Normal Control (Group-I) animals. Group-III treated by Levodopa/Carbidopa (125mg/kg p.o.) showed significant increase in locomotor activity at 7th day as compared to Negative Control (Group-II). Test 1 (Group-IV) treated by low dose of thiocolchicoside (4mg/kg p.o) showed significant increase in the locomotor activity at 7th day as compared to Negative Control (Group-II). Test 2 (Group-V) treated by high dose of thiocolchicoside (8mg/kg p.o) showed significant increase in the locomotor activity at 7th day as compared to Negative Control (Group-II).
Table 5. Effect of Thiocolchicoside on locomotor activity (Day 14)
|
Groups |
Treatment (Dose) |
Number of Locomotor activity in 10 min |
|
Group I (Normal Control) |
Vehicle (10 ml/kg) |
392±37.8 |
|
Group II (Negative Control) |
Haloperidol (1 mg/kg) |
183±16.2
|
|
Group III (Positive Control) |
Haloperidol (1 mg/kg) + Levodopa/Carbidopa (125 mg/kg) |
302±28.5 |
|
Group IV (Test-1) (Low Dose) |
Thiocolchicoside (4mg/kg) + Haloperidol (1 mg/kg) |
297±25.9 |
|
Group V (Test-2) (High Dose) |
Thiocolchicoside (8mg/kg) + Haloperidol (1mg/kg) |
276±25.3 |
All values are expressed as mean ± SEM; n=6 rats in each group, data was analysed by one way ANOVA followed by Dunnetts ‘t’ test. *p<0.05, **p<0.01, ***p<0.001.
In table-5, the Negative Control (Group-II) Haloperidol (1mg/kg i.p.) administration showed significant reduction in the locomotor activity as compared to Normal Control (Group-I) animals. Group-III treated by Levodopa/Carbidopa (125mg/kg p.o.) showed significant increase in locomotor activity at 14th day as compared to Negative Control (Group-II). Test 1 (Group-IV) treated by low dose of thiocolchicoside (4mg/kg p.o) showed more significant increase in the locomotor activity at 14th day as compared to Negative Control (Group-II). Test 2 (Group-V) treated by high dose of thiocolchicoside (8mg/kg p.o) showed significant increase in the locomotor activity at 14th day as compared to Negative Control (Group-II).
Table 6. Effect of Thiocolchicoside on locomotor activity (Day 21)
|
Groups |
Treatment (Dose) |
Number of locomotor activity in 10 min |
|
Group I (Normal Control) |
Vehicle (10ml/kg) |
395±37.6
|
|
Group II (Negative Control) |
Haloperidol (1 mg/kg) |
170±15.1
|
|
Group III (Positive Control) |
Haloperidol (1 mg/kg)+ Levodopa/Carbidopa (125mg/kg) |
316±29.4 |
|
Group IV (Test-1) (Low Dose) |
Thiocolchicoside (4mg/kg)+ Haloperidol (1 mg/kg) |
311±28.7 |
|
Group V (Test-2) (High Dose) |
Thiocolchicoside (8mg/kg)+ Haloperidol (1mg/kg) |
271±24.8 |
All values are expressed as mean ± SEM; n=6 rats in each group, data was analysed by one way ANOVA followed by Dunnetts ‘t’ test. *p<0.05, **p<0.01, ***p<0.001.
In table-6, the Negative Control (Group-II) Haloperidol (1mg/kg i.p.) administration showed significant reduction in the locomotor activity as compared to Normal Control (Group-I) animals. Group-III treated by Levodopa/Carbidopa (125mg/kg p.o.) showed significant increase in locomotor activity at 21st day as compared to Negative Control (Group-II). Test 1 (Group-IV) treated by low dose of thiocolchicoside (4mg/kg p.o) showed more significant increase in the locomotor activity at 21st day as compared to Negative Control (Group-II). Test 2 (Group-V) treated by high dose of thiocolchicoside (8mg/kg p.o) showed significant increase in the locomotor activity at 21st day as compared to Negative Control (Group-II).
Figure 1. Effect of Thiocolchicoside on Dopamine level
Interpretation:
The Negative Control (Group-II) Haloperidol (1mg/kg i.p.) administration showed significant reduction in the dopamine level as compared to Normal Control (Group-I) animals. Group-III treated by Levodopa/Carbidopa (125mg/kg, p.o.) showed significant increase in the dopamine level as compared to Negative Control (Group-II). Test 1 (Group-IV) treated by low dose of thiocolchicoside (4mg/kg p.o) showed significant increase in the dopamine level as compared to Negative Control (Group-II). Test 2 (Group-V) treated by high dose of thiocolchicoside (8mg/kg p.o) showed significant increase in the dopamine level as compared to Negative Control (Group-II).
DISCUSSION:
The loss of dopamine-producing neurons in the ventral midbrain and the cell bodies that project to the striatum in the substantia nigra pars compacta (SNpc) is the hallmark of Parkinson's disease (PD), a neurodegenerative disease. The primary cause of this illness is the nigrostriatal pathway degeneration, which lowers dopamine levels in the striatum and causes motor abnormalities like bradykinesia, akinesia, resting tremor, and muscle rigidity1,8. This study demonstrated that giving GABA mimetics can lessen catalepsy brought on by the antipsychotic medication haloperidol. The present study shows that the protective effect of thiocolchicoside against increase in vacuous chewing movements (VCMs) and catalepsy causes due to the haloperidol. Humans with neuroleptics experiences two primary motor disturbances: tardive dyskinesia and catalepsy together referred to as extrapyramidal side effects which is reduced by the administration of the centrally acting GABA mimetic drug thiocolchicoside. Dopamine D2 receptor inhibition is a primary or indirect cause of several illnesses. These adverse effects are the primary drawbacks for the therapeutic use of conventional neuroleptics. Haloperidol treatment for 21 consecutive days caused a substantial increase in VCMs and tongue protrusion in rats, indicating orofacial dyskinesia. This is further supported by a previous study in which rats given haloperidol (1mg/kg, i.p) once a day in the morning for 21 successive days produces orofacial movements such as tongue protrusion and VCMs. The reported literature has noted that long-term use of neuroleptics may cause an imbalance in the generation and cleansing of free radicals. This has a role in initiating hyperkinetic movements inside the orofacial region2,9,10. A blockage of postsynaptic striatal dopamine D1 and D2 receptors causes due to the typical neuroleptic-induced catalepsy. Despite this evidence, a number of other neurotransmitters, including serotonin, GABA, and acetylcholine have also been dysfunction. Apart from the dysfunction of several neurotransmitters in catalepsy, numerous preclinical and clinical investigations have indicated the potential role of reactive oxygen species in the toxicity caused by haloperidol. The current investigation also revealed that the group treated with haloperidol experienced a rise in oxidative stress as compared to the normal vehicle treated group, indicating that haloperidol may have neurotoxic effects11. Postsynaptic striatal dopamine D1 and D2 receptor blockage has been related to neuroleptic-induced catalepsy12. Strong antagonistic action on dopamine receptors (mostly D2), particularly in the brain's mesolimbic and mesocortical systems, is how haloperidol gets its antipsychotic effects. Dopamine's actions can be inhibited by haloperidol. It has a stronger binding to the dopamine D2 receptor than dopamine itself. Haloperidol is believed to abolish dopamine neurotransmission by competitively blocking postsynaptic dopamine (D2) receptors in the brain. It mostly affects D2 receptors, with little effects also seen on 5-HT2 and α1 receptors, and very little action on dopamine D1 receptors. The medication also partially inhibits the autonomic nervous system's α-adrenergic receptors13,14,15. Haloperidol is neurotoxic when administered long-term to neuroleptic patients because it alters the mitochondrial electron transport chain, which results in oxidative stress. From the observations of above studies the anticataleptic effects of thiocolchicoside is seen in haloperidol model of catalepsy in rats. Rats with neuroleptic-like catalepsy caused by haloperidol are utilized to assess the antiparkinsonian effects of the drugs. In this investigation, the effectiveness of thiocolchiocoside is observed in haloperidol-induced catalepsy in rats15. Thiocolchicoside functions as an efficient muscle relaxant because it has a strong and selective affinity for g-aminobutyric acid A (GABA-A) receptors. By activating GABA inhibitory pathways, it influences muscular contractions16.
In the high bar test the cataleptic score was increased in haloperidol (1mg/kg, i.p) administered rats as compared to Normal Control group. In the Negative Control (Group-II) there is significantly elevated catalepsy with sign increase in paw retention time on bar. Test 1 (Group-IV) treated by low dose of thiocolchicoside (4mg/kg, p.o) showed more significant reduction in the cataleptic activity at 14th and 21st day. Test 2 (Group-V) treated by high dose of thiocolchicoside (8mg/kg, p.o) showed significant reduction in the cataleptic activity at 14th and 21st day. The cataleptic activity significantly decreases in test 1 (Group-IV) treated by low dose of thiocolchicoside (4mg/kg) as compared with the test 2 (Group-V) treated by high dose of thiocolchicoside (8mg/kg).
In actophotometer the locomotor activity was decreased in haloperidol (1 mg/kg, i.p) administered rats as compared to normal control (Group-I). Group-III treated by Levodopa/Carbidopa (125mg/kg, p.o.) showed significant increase in locomotor activity at 7th and 14th day and more significant increase in locomotor activity at 21st day. Test 1 (Group-IV) treated by low dose of thiocolchicoside (4mg/kg, p.o) showed more significant increase in the locomotor activity at 14th and 21st day. Test 2 (Group-V) treated by high dose of thiocolchicoside (8mg/kg, p.o) showed significant increase in the locomotor activity at 7h and 14th day.
We looked at the anticataleptic properties of various thiocolchicoside dosages. The findings demonstrated that thiocolchicoside had a greater anticataleptic effect at a dose of 4 mg/kg than at an 8mg/kg. Conversely, thiocolchicoside's anticataleptic efficacy was lessened when the dosage was raised.
Haloperidol (1mg/kg, i.p) treated animals shows decreases the dopamine level. Group-III treated by Levodopa/Carbidopa (125mg/kg p.o.) showed more significant increase in dopamine level. Group IV and Group-V did not significantly increase dopamine level. This study revealed a significant anticataleptic effect of thiocolchicoside in experimental model of parkinsonism induced by haloperidol in rats.
CONCLUSION:
It can be concluded that the thiocolchicoside may possess anticataleptic effect. The effect was more prominent when animals treated with the low dose of thiocolchicoside (4mg/kg, i.p). Our findings indicate that thiocolchicoside treatment improves catalepsy. Furthermore, we propose its potential application as an adjuvant therapy to enhance the effectiveness of anti-Parkinson's medications. Based on the findings of previous research, it is possible that thiocolchicoside's ability to prevent Parkinson's disease symptoms, such as catalepsy, is caused by the regulation of neurotransmitters like glutamate, serotonin, and dopamine, which are known to have antioxidant and catalepsy-prevention effects. However further investigation is required to establish this neuroprotective response in another experimental animal model.
REFERENCES:
1. Prakash Kumar Mahilange. Effective Supply Chain Management Equilibrates the Supply and Demand Management of an Organization. Asian J. Management. 2016; 7(3): 231-235.
2. Ruchita Pangriya, Rupesh Kumar M. Factors Affecting the Performance of Private Label Brands in Indian Online Market: an Assessment of Reliability and Validity. Asian J. Management. 2016; 7(3): 223-230.
3. Ajay Jamnani. E-Commerce: Big Billion Day – A case study with special reference to Flipkart. Asian J. Management. 2016; 7(3): 219-222.
4. M. Rupesh Kumar, A.G.V. Narayanan. Whether Shoppers of Tier I City are aware about Multi-Brand Outlets? Asian J. Management. 2016; 7(3): 176-184.
5. Partha Prasad Chowdhury. Relationship between Opportunism and Trust: An Empirical Study in the Automobile Sector of India. Asian J. Management. 2016; 7(3): 185-192.
6. GoutamTanty, P K Patjoshi. A Study on Stock Market Volatility Pattern of BSE and NSE in India. Asian J. Management. 2016; 7(3): 193-200.
7. Yosef Latifi, Fariba Azizzadeh, Samira Azizzadeh. An intellectual capital model for Dey bank employees. Asian J. Management. 2016; 7(3): 159-163.
8. Elangovan N. Design quality of Mobile trading system application software for Smartphones. Asian J. Management. 2016; 7(3): 207-212.
9. Ashok Kumar Jha, G. K. Deshmukh, Sanskrity Joseph. Customers Intention to Switch towards Mobile Number Portability in Chhattisgarh – A Study Harsh Vineet Kaur. Asian J. Management. 2016; 7(3): 213-218.
10. Harsh Vineet Kaur. Can MUDRA Bank be a Game Changer for India?. Asian J. Management. 2016; 7(4): 247-250.
11. Vinod Nair, Albina Arjuman, P. Dorababu, H.N. Gopalakrishna, et al. Effect of NR-ANX-C (a polyherbal formulation) on haloperidol induced catalepsy in albino mice. Indian J Med Res 126, November 2007, 480-484.
12. Sudhakar Pemminati, Gopalakrishna HN, Ashok Varma K,et al. Effect of acute administration of ursolic acid on haloperidol induced catalepsy in mice. Journal of Pharmacy Research 2011; 4(8): 2608-2609.
13. Anita Verma and S.K. Kulkarni. D1/D2 dopamine and N-methyl-D-aspartate (NMDA) receptor participation in experimental catalepsy in rats. Psychopharmacology. 1992; 109: 477-483.
14. Sanjay B. Kasture, Mayur Gaikar, Veena Kasture, et al. Tea component, epigallocatechin gallate, potentiates anticataleptic and locomotor-sensitizing effects of caffeine in mice. Behavioural Pharmacology. 2015; 26(1 and 2).
15. P. Jayachandra Reddy, V. Prabhakaran, K. Umasankar, M. Sekar Babu. Anti- cataleptic activity of ethanol extract of Vernonia Cinerea L. Asian Journal of Pharmaceutical Science and Technology. 2012; 2(10: 23-29.
16. Mario Carta, Luca Murru, et al. The muscle relaxant thiocolchicoside is an antagonist of GABAA receptor function in the central nervous system. Neuropharmacology. 2006; 51: 805-815.
17. M.L.G. Wadenberg, K.A. Young, et al. Effects of local application of 5-hydroxytryptamine into the dorsal or median raphe nuclei on haloperidol-induced catalepsy in the rat. Neuropharmacology. 1999; 38: 151 – 156.
18. Sanjay Kastureu, Shrikant Barhateu, Mahalaxmi Mohan, et al. Caffeine withdrawal retains anticataleptic activity but Withania somnifera withdrawal potentiates haloperidol-induced catalepsy in mice. Natural Product Research. 2009; 23(80; 724-728.
19. Manoj K. Aswar, Rujuta H. Joshi. Anti-cataleptic activity of various extracts of ocimum sanctum. International Journal of Pharma Research and Development. 2010; 2(6).
20. Sneha Nawale, P. Pranusha, K. Padma Priya, M. Ganga Raju. Evaluation of Anti-cataleptic activity for methanolic extract of Aerva Lanata whole plant. Journal of Pharma Research. 2019;8(7).
Received on 24.07.2024 Modified on 14.08.2024
Accepted on 30.08.2024 ©AJRC All right reserved
Asian J. Research Chem. 2024; 17(4):230-236.