الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive and behavioral components. It is the displeasing feeling of fear and concern. Anxiety is considered to be a normal reaction to a stressor. It may help an individual to deal with a demanding situation by prompting them to cope with it.
When anxiety becomes excessive, it may fall under the classification of an anxiety disorder. Anxiety disorders are among the most prevalent mental disorders in the general population. Where, women affected nearly twice as frequently as men.
These disorders are frequently treated using benzodiazepine and non-benzodiazepine anxiolytics. These anxiolytics should be prescribed for short periods only with the frequency and duration of use customized to each patient’s circumstances.
Benzodiazepine anxiolytics (ex. Diazepam) are most useful for short term treatment in promoting sleep. However, long term use may lead to adverse effects and withdrawal phenomena, such as; sleepiness and reduced alertness. In contrast, the newer generation non-benzodiazepine anxiolytics (ex. Zaleplon) have no significant adverse effects and withdrawal phenomena when taken as recommended, making them the best first line choice for long term treatment of anxiety.
Some of natural products (ex. Kava) and non-benzodiazepine anxiolytics have largely replaced the benzodiazepine anxiolytics for anxiety treatment due to low risk of tolerance, dependence and residual central nervous system effects compared with benzodiazepine anxiolytics. Consequently, these benefits of natural products and non-benzodiazepine anxiolytics encourage the patients to take overdose of this type of anxiolytics leading to drug abuse.
The present study was designed to investigate the toxicological overdose effect of some anxiolytic drugs on different vital organs in experimental animals by using several parameters and to study the probable mechanism(s) of action of these anxiolytic drugs. In addition, we performed histopathological examination on vital organs of experimental animals to record any pathological changes occurred from these anxiolytics’ abuse.
• The main findings of the present study can be summarized as follows:
A- For the motor co-ordination assay:
1- Oral administration of diazepam 1 and 4 mg/kg daily for four weeks to adult male albino rats produced a significant decrease on rotarod performance evidenced by a significant decrease on rotarod balancing time comparing to control group values. Whereas, the effect on rotarod performance is more predominant by diazepam 4 mg/kg.
2- Oral administration of zaleplon 1 mg/kg daily for four weeks to adult male albino rats produced no change on rotarod performance evidenced by no change on rotarod balancing time in comparison with that of control group values.
3- Oral administration of zaleplon 4 mg/kg daily for four weeks to adult male albino rats induced a significant decrease on rotarod performance evidenced by a significant decrease on rotarod balancing time comparing to control group values.
4- Oral administration of kava kava 100 and 400 mg/kg daily for four weeks to adult male albino rats showed no change on rotarod performance evidenced by no change on rotarod balancing time as compared with control group values.
B- For the anxiety performance assay:
1- Oral administration of diazepam 1 and 4 mg/kg daily for four weeks to adult male albino rats produced a significant decrease in anxiety performance comparing to control group values. Whereas, the effect on anxiety performance is more extent by diazepam 4 mg/kg.
2- Oral administration of zaleplon 1 and 4 mg/kg daily for four weeks to adult male albino rats performed a significant decrease in anxiety performance in comparison with that of control group values. Whereas, the effect on anxiety performance is more potent by zaleplon 4 mg/kg.
3- Oral administration of kava kava 100 and 400 mg/kg daily for four weeks to adult male albino rats showed a significant decrease in anxiety performance as compared with control group values. Whereas, the effect on anxiety performance is more predominant by kava kava 400 mg/kg.
C- For the heart rate and blood pressure assay:
1- Oral administration of diazepam 1 and 4 mg/kg daily for four weeks to adult male albino rats caused a significant decrease on heart rate and blood pressure comparing to control group values. Whereas, the effect on heart rate and blood pressure is more predominant by diazepam 4 mg/kg.
2- Oral administration of zaleplon 1 mg/kg daily for four weeks to adult male albino rats produced no change on heart rate and blood pressure in comparison with that of control group values.
3- Oral administration of zaleplon 4 mg/kg daily for four weeks to adult male albino rats induced a significant decrease on heart rate and blood pressure comparing to control group values.
4- Oral administration of kava kava 100 and 400 mg/kg daily for four weeks to adult male albino rats showed no change on heart rate and blood pressure as compared with control group values.
D- For brain neurotransmitters (Free amino acids and monoamines) assay:
1- Oral administration of diazepam 1 mg/kg daily for four weeks to adult male albino rats caused no change on glutamic acid and nor-epinephrine and induced significant decrease on aspartic acid and produced significant increase on GABA, dopamine and serotonin comparing to control group values.
2- Oral administration of diazepam 4 mg/kg daily for four weeks to adult male albino rats showed significant decrease on glutamic acid, aspartic acid and nor-epinephrine and induced significant increase on GABA, dopamine and serotonin as compared with control group values.
3- Oral administration of zaleplon 1 mg/kg daily for four weeks to adult male albino rats performed no change on glutamic acid, aspartic acid, GABA, nor-epinephrine, dopamine and serotonin comparing to control group values.
4- Oral administration of zaleplon 4 mg/kg daily for four weeks to adult male albino rats induced no change on glutamic acid, aspartic acid, nor-epinephrine and dopamine and caused significant increase on GABA and serotonin as compared with control group values.
5- Oral administration of kava kava 100 mg/kg daily for four weeks to adult male albino rats performed no change on glutamic acid, aspartic acid, GABA, nor-epinephrine, dopamine and serotonin comparing to control group values.
6- Oral administration of kava kava 400 mg/kg daily for four weeks to adult male albino rats caused no change on aspartic acid and nor-epinephrine and induced significant decrease on glutamic acid and produced significant increase on GABA, dopamine and serotonin in comparison with that of control group values.
E- For the hepatotoxicity assay:
1- Oral administration of diazepam 1 mg/kg daily for four weeks to adult male albino rats produced no change on serum direct billirubin and induced significant decrease on serum total protein and caused significant increase on ALT & AST activities and serum total billirubin comparing to control group values.
2- Oral administration of diazepam 4 mg/kg daily for four weeks to adult male albino rats showed significant decrease on serum total protein and induced significant increase on ALT & AST activities, serum direct billirubin and serum total billirubin as compared with control group values.
3- Oral administration of zaleplon 1 mg/kg daily for four weeks to adult male albino rats performed no change on ALT activity, serum total protein, serum direct billirubin and serum total billirubin and induced significant increase on AST activity comparing to control group values.
4- Oral administration of zaleplon 4 mg/kg daily for four weeks to adult male albino rats induced significant decrease on serum total protein and showed significant increase on ALT & AST activities, serum direct billirubin and serum total billirubin as compared with control group values.
5- Oral administration of kava kava 100 mg/kg daily for four weeks to adult male albino rats performed no change on ALT & AST activities, serum total protein, serum direct billirubin and serum total billirubin comparing to control group values.
6- Oral administration of kava kava 400 mg/kg daily for four weeks to adult male albino rats caused no change on serum total billirubin and induced significant decrease on serum total protein and produced significant increase on ALT & AST activities and serum direct billirubin in comparison with that of control group values.
F- For the nephrotoxicity assay:
1- Oral administration of diazepam 1 mg/kg daily for four weeks to adult male albino rats showed no change on blood urea nitrogen and induced significant increase on serum creatinine levels comparing to control group values.
2- Oral administration of diazepam 4 mg/kg daily for four weeks to adult male albino rats caused significant increase on blood urea nitrogen and serum creatinine levels as compared with control group values.
3- Oral administration of zaleplon 1 mg/kg daily for four weeks to adult male albino rats performed no change on blood urea nitrogen and serum creatinine levels comparing to control group values.
4- Oral administration of zaleplon 4 mg/kg daily for four weeks to adult male albino rats induced no change on blood urea nitrogen and led to significant increase on serum creatinine level as compared with control group values.
5- Oral administration of kava kava 100 and 400 mg/kg daily for four weeks to adult male albino rats produced no change on blood urea nitrogen and serum creatinine levels comparing to control group values.
G- For the body weight assay:
1- Oral administration of diazepam 1 and 4 mg/kg daily for four weeks to adult male albino rats caused a significant increase in body weight comparing to control group values. Whereas, the effect on body weight is more extent by diazepam 4 mg/kg.
2- Oral administration of zaleplon 1 and 4 mg/kg daily for four weeks to adult male albino rats performed a significant increase in body weight in comparison with that of control group values. Whereas, the effect on body weight is more predominant by zaleplon 4 mg/kg.
3- Oral administration of kava kava 100 mg/kg daily for four weeks to adult male albino rats showed no change on body weight as compared with control group values.
4- Oral administration of kava kava 400 mg/kg daily for four weeks to adult male albino rats showed a significant increase in body weight as compared with control group values.
• Depending on the previously summarized results, it may be concluded that:
- For long term of administration:
1- Diazepam is a good anxiolytic, but it has a lot of adverse effects, such as; decrease in muscle co-ordination, increase in body weight, decrease in heart rate and blood pressure, alterations in liver functions leading to severe hepatotoxicity and alterations in kidney functions leading to moderate nephrotoxicity.
2- Zaleplon is a potent anxiolytic, however it has many side effects like diazepam but with a lesser extent significantly.
3- Kava kava is a mild anxiolytic and it has been safer than diazepam and zaleplon because of its safety on heart, liver and kidney.
Therefore, for long term of administration; zaleplon is considered as the drug of choice for treatment of anxiety in comparison with that of diazepam and kava kava as anxiolytics regarding to anxiety performance and adverse effects.