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Contents of Volume 1, No.2 2005 | Download PDF file for Print

EFFECT OF ATYPICAL ANXIOLYTIC DRUG ON STRESS INDUCED BEHAVIOR

Rafeeq Alam Khan, Saima Afzal Siddiqui, Iqbal Azhar¹, Shahida P. Ahmed
Department of Pharmacology, Faculty of Pharmacy, University of Karachi-75270
¹Department of Pharmacognosy, Faculty of Pharmacy, University of Karachi-75270, Pakistan

ABSTRACT

Leaves of Tamarindus indica were extracted in absolute methanol and n-butanol. Emesis was induced by the oral administration of copper sulfate (l0 mg/ml). Both extracts were tested for their anti-emetic potential. Results showed that both of these extracts have anti-emetic activity when compared with chlorpromazine. However methanol extract has more pronounced anti-emetic potential.

Keywords: Tamarindus indica, methanol extract n-butanol extract, anti-emetic activity.

INTRODUCTION

Nausea and vomiting may be manifestation of a wide variety of conditions, including pregnancy, motion sickness, gastrointestinal obstruction, peptic ulcer, drug toxicity, myocardial infarction, renal failure, and hepatitis. Nausea and vomiting can follow the administration of many drugs particularly cancer chemotherapeutic agents. These symptoms may occur upon emergence from general anesthesia and often accompany infectious and noninfectious gastrointestinal disorders. In cancer chemotherapeutic, drug induced nausea and vomiting may occur so regularly that anticipatory vomiting occurs when patient return for treatment before the chemotherapeutic agent is given. If not controlled, the discomfort associated with drug induced emesis may cause a patient to refuse further chemotherapy (Brunton 1991; Altman 1998). Selection of adequate animal model in determining the anti-emetic activity of natural product is difficult. The Sclerotia of Poria cocos wolf (Polyporaceae) i.e. hoelen, one of the well known Chinese traditional medicine has an anti-emetic effect on pigeons treated with digitoxin (Su 1977). Anti-emetic principles from Mangnolia obovata bark, Zingiber officinale rhizome (Kawai et al., 1994), Inula linariaefolia flowers and Forsythia suspnsa fruits (Kinoshita et al., 1996) and Poria cocos (Tai 1995) were reported using frogs as test subjects. The long emetic latency of frogs induced by emetic agent was not suitable for testing many samples within short period of tine. Therefore we studied another screening method using young chicks for anti-emetic activity (Akita 1998 & Yang et al., 1999) to overcome these difficulties.

In this study, we have demonstrated the potential of anti-emetic activity in the extracts of Tamarindus indica. Effect produced by principles of Tamarindus indica is determined by the decrease in the numbers of retching after oral administration of copper sulfate. Young male chicks were used as test animals.

MATERIALS AND METHODS

Material

The fresh leaves of Tamarindus indica (Tamarind) were collected form Karachi, Pakistan during the month of April 2001. The sample was identified by Khalida Khatoon and Voucher specimen (K-97-15C) was deposited in the Herbarium, Department of Botany, University of Karachi.

Animals

Young male chicks (Arberacer) 4 days of age, weighing from 32-52 g were taken from Surban Poultry Breeding Farm, Karachi, Pakistan.

Bio-assay of anti-emetic activity

In present study, the antiemetic activity was determined by calculating the mean decrease in number of retching in contrast with those of control (Yang et al., 1999). The animals were divided into 4 groups, each group having 7 animals. Each chick was set aside for 10 min to stabilize in large beaker. The test and standard drugs were administered at 150 mg/kg abdominally. Control group received only saline 0.9%. After 10 min copper sulfate was administered orally at 50 mg/kg, then the number of retching (an emetic action without emeting gastric material) was observed during next 10 min. The criteria of antiemetic potential were decrease in number of retching in contrast with those of control. The percent inhibition was calculated by the following formula:

Inhibition (%) =A—B/A(x 100)

Where
A = control frequency of retching
B = frequency of retching after sample treatment

Statistical Analysis

Value for antiemetic activity was expressed as mean ± S.E.M. The statistical significance of the difference was determined by an unpaired Student’s t-test.

Preparation of extract

Leaves were dried in shade at 21-30oC for 15-30 days. These parts were then chopped and ground. Chlorpromazine, methanol and n-butanol extracts of Tamarindus indica were dissolved in 0.9% saline containing 5% DMSO and 1% Tween 80 and administered abdominally at a volume of l0 ml/kg to the test animals on the basis of their body weights.

RESULTS AND DISCUSSION

Results of the antiemetic activity of chlorpromazine and two extracts (methanol and n-butanol) of Tamar¬indus indica are shown in table 1.

Both extracts of Tamarindus indica inhibited emesis to an extant greater than Chlorpromnazine at 150 mg/kg (Fig 1). Methanol extract has more pronounced effect on emesis.

Methanol and n-butanol extracts showed 69.48 and 49.48% inhibition as compare with Chlorpromazine that showed 32.99% inhibition at p<0.05.

Tamarindus indica was selected for the present study because of its ayurvedic reputation and some previously reported biological activities [Iida et al. (1978); Rimbau et al. (l999); Gidley et al. (1991); Lakshmanan and Naryanan (1990); Lanhers et al. (1996); El-Tahir et al. (1998); Mustapha et al. (1996); Ali et al. (1998); Burgalassi et al. (1999); Cavagna (1996); De et al. (1999); Mastro¬marino et al. (1997); Sambaiah and Srinivasan (1989); Sinibaldi et al. (1992); Sone et al. (1992); Sreelekha et al. (1993); Strick¬land et al. (1999) and Veena and Jayaprakash (1999)]. By now, however, nothing had been done to determine its antiemetic activity. But Tama¬rindus indica is used traditionally to control the nausea and vomiting in South Asian countries like Pakistan and India.

In present study the two extracts of Tamarindus indica (methanol and n-¬butanol) were selected to determine anti-emetic activity. Results show that, both extracts of Tamarindus indica have anti-emetic potential (Table 1). Results of both groups (methanol and n¬-butanol) were comparable with that of chlorpromazine, the reference drug. The methanol extract of Tamarindus indica has more significant antiemetic potential than butanol extract.

Although the results are significant and comparable with that of Chlorpromazine but the mode of action is not known. And also these results need to be verified in other experimental models Pharma¬codynamics studies should also be undertaken to establish the mechanism of action of these plant extracts.

ACKNOWLEDGEMENT

The authors would like to thank Surban Poultry Breeding Farm, Karachi, Pakistan for providing the animals used in this study.

RESULTS AND DISCUSSION

Anxiety disorders are a class of illness associated with unreasonable and disturbing sensation of fear and tension. When an individual can not cope up with the persisting tension, it’s state changes to anxiety. There are several types of anxiety disorders, such as panic disorder, agoraphobia, specific Phobia, Social Phobia, Obsessive-Compulsive Disorder (OCD), Post-Traumatic Stress Disorder and Generalized Anxiety Disorder. Common symptoms during anxiety disorder include unrealistic or excessive worry, sleep disturbances, dizziness, tiredness, racing/pounding heart, upset stomach, numbness in hands and face or feet and Fatigue (Gillin and Byerly, 1990).

Buspirone is helpful for generalized anxiety. The food and drug administration has approved its use for anxiety with mild depressed mood. Early research indicates it may also help social phobias and can be used in combination with other medications for OCD. Buspirone is much less likely than the benzodiazepines to cause drowsiness and fatigue. It is very safe medication, not habit-forming, and there are no withdrawal symptoms (Eison and Temple 1986). Buspirone produce significant changes in several stress induced parameters.

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