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International Journal of Technical Research(IJTR)Vol. 2, Issue 1, Mar-Apr 2013
COMBINED STUDY OF ATENOLOL AND ESCITALOPRAM ON ANXIETY AND Gulshan Sindhwani ABSTRACT
of people who commit suicide have Major depressive disorder is a depression or another mood disorder. DRUG PROFILE
encompassingaccompanied by 1. Escitalopram
in normally enjoyable activities. escitalopram is 10 mg once daily for the In the animal study we found that drugs treatment of depression or generalized significantly reduced the anxiety, The anxiety disorder. However, if symptoms combination of two drugs i.e. atenolol and continue or if side effects occur during the escitalopram were taken and by using the treatment process, one have to alter elevated plus maze (EPM) apparatus, the dosage. Escitalopram may be taken with or dose of drugs was compared to the control without food, but should be taken at the group and standard escitalopram. The same time each day to maintain an even level of the drug in blood. significant as compared to control value of 2 ATENOLOL
p was found (p=0.008). EPM was used to Atenolol is a selective observe the anti anxiety of drug on the rats abelonging to the group the dose of the drug was compare from of (sometimes written vehicle treated to time spent in open arm of a class of drugs used primarily a rats was increasing which shown that in Introduced in drug is having anxiolytic activity. 1976, atenolol was developed as a The term "major depressive disorder" was treatment of The chemical works by slowing down the heart and to designate this reducing its workload. Unl as a in the 1980 atenolol does not pass through the blood- brain barrier thus avoiding va and has become widely used since. The MATERIAL AND METHOD
general term depression is often used to Elevated Plus Maze
denote the disorder; but as it can also be Elevated Plus Maze (EPM) test (Pellow et used in reference to other al.,1985) for studying the anxiolytic effect it is disfavored in rodents was used. EPM consists of two over more precise terminology for the open arms (15cm x10 cm) and two closed disorder in clinical and research use. Major arms (50 cm x 10 cm x 40 cm) with an depression is a disabling condition which open roof and elevated at 50 cm. 1 hour adversely affects a person's family, work after the oral administration of drugs, the or school life, sleeping and eating habits, rat was placed in centre of the maze, facing and general health. In the United States, one closed arm. During a 5 min test period around 3.4% of people with major the following measures were taken: depression commitand up to 60% the time spent in the open and closed arms; total number of arm entries. International Journal of Technical Research(IJTR)
Vol. 2, Issue 1, Mar-Apr 2013
International Journal of Technical Research(IJTR)
Vol. 2, Issue 1, Mar-Apr 2013
Treatment Schedule
Table: 1. Elevated Plus Maze (EPM) test groups with their treatment schedule:
administration and duration (14 days). water 1 ml/kg p.o Atenolol+Escitalopram 0.5 mg/kg+1 mg/kg p.o
n = number of animals used in each group.
. Treatment duration = 14 days.
Forced swimming test (FST)
The procedure as described by (Porsolt et al., 1978) was used, except that the water level
was deeper (Detke and Lucki, 1996). Swimming sessions were conducted by placing rats in
individual glass cylinders (45 cm high×20 cm in diameter) containing (25±2 °C) water 38
cm deep, so rats could not support themselves by touching the bottom with their feet.
Two swimming sessions were performed between 12:00 h and 19:00 h, an initial 15 min
pretest followed 24 h later by a 5 min test. The immobility period in seconds was measured
live in each test session by a blind observer.
Table: 2. Forced swimming test (FST) groups with their treatment schedule:
duration (14 days). Distilled water (vehicle) Atenolol+Escitalopram 0.5 mg/kg+1 mg/kg p.o n=4 no of animal used
Experimental methods
The animals of either sex were selected randomly of uniform weight 120±5 gm from animal
house. The room temperature was maintained 22±2°C with food (Lipton India Ltd. pellets)
and water ad libitum. The animals were transferred to the laboratory at least 1h before the
start of the experiment. The experiments were performed during day (08:00-16:00 h). The
institutional animal ethical committee approved to the study protocol.
Result and Discussion
Elevated plus maze (EPM) model
Table: 3. Elevated Plus Maze
Time spent in open (p.o for 14 days) International Journal of Technical Research(IJTR)
Vol. 2, Issue 1, Mar-Apr 2013
Escitalopram+Atenolol F= 6.38, p=0.008* compare to respective vehicle control group Values are mean ± SEM of observation In the animal study we found that drugs significantly reduced the anxiety, the result was
shown in table, two drugs and its combination were taken and observed in elevated plus
maze apparatus the dose of drugs was compared to the control group and standard
escitalopram. The result of combination was found significant as compared to control value
of p was found (p=0.008). EPM was used to observe the anti anxiety of drug on the rats the
dose of the drug was compare from vehicle treated to time spent in open arm of a rats was
increasing which shown that drug is having anxiolytic activity.
Modified forced swim test
Table 4 modified forced swim test
Values are mean ± SEM of observation
The table illustrates the effect of drugs on the duration of immobility time in the MFST
model, one way ANOVA revealed that there were significant differences between treatment
Time of immobility (Mean± (p.o for 14 days) Escitalopram+atenolol groups F=10.77,p=0.001 from the vehicle treated group drugs and in combination
significantly decresed the duration of immobility time indicating anti depressant effect.
DISCUSSION
The modified FST, beside allowing to Atenolol alone and in combination with observe the effects of SSRIs in rats also escitalopram (SSRI) in modified FST in provides a unique tool to understand the rats enhanced climbing behavior while AD like effect of both serotonergic and catecholaminergic ADs and to detect the swimming significantly. Escitalopram is S- effects of novel types of ADs compounds enantiomer of citalopram which is reported (Maciej et al., 2007; Cryan et al., 2002; to increase swimming behavior at the cost 2005). The critical influence of LC NE of climbing and immobility (Maciej et al., neurons on mobility of rats in FST is well 2007). Belonging to the same class, established (West, 1990; Aghajanian et al., escitalopram also increased swimming 1997; Klimek et al., 1997). An increase in significantly. The mechanism involved is LC activity decreases mobility, while increase in 5-HT synaptic concentration, reduction in the activity has the opposite effect. Thus, it can be assumed that a neurotransmission, which is well known. decrease in LC activity could be associated with antidepressant activity of atenolol. International Journal of Technical Research(IJTR)
Vol. 2, Issue 1, Mar-Apr 2013
Thus, the combination of atenolol with [III] Frodl, T. and Meisenzahl, E.M. (2003). Larger amygdala volumes in first depressive episode as compared to escitalopram offers advantage over the recurrent major depression and healthy control subjects. individual administration of these drugs on Biol Psychiatry. 53:338 –344. [IV] Drevets, W.C. and Bogers, W. (2002). Functional anatomical correlates of antidepressant drug treatment The elevated plus maze (EPM) is a widely assessed using PET measures of regional glucose metabolism. Eur Neuropsychopharmacol 12:527–544. used behavioral assay for rodents that has Soares, J.C. and Mann, J.J. (1997). The anatomy of mood been validated to assess the anti-anxiety disorders—review of structural neuroimaging studies. [Comment]. Biological Psychiatry. 41:86 –106. effects of a variety of pharmacological [VI] Artigas, F. and Romero, L. (1996). Acceleration of agents & to define brain regions and theeffect of selected antidepressant drugs in major depression by 5-HT1A antagonists. Trends Neurosci. mechanisms underlying anxiety-related behavior. Anti-anxiety agents exhibit an [VII] Mitchell, P.J. and Redfern, P.H. (1997). Potentiation of the time-dependent, antidepressant-induced changes in the increase in the percentage preference to agonistic behaviour of resident rats by the 5-HT1A open arms, the number of entries and time receptor antagonist, WAY-100635. Behav Pharmacol. 8:585– 606. spent in open arms. In our study, we [VIII] Blier, P. and Bergeron, R. (1998). The use of pindolol to observed a significant increase in the potentiate antidepressant medication. J Clin Psychiatry. 59:16 –23. percentage preference to open arms, the [IX] Mewshaw, R.E. and Zhou, D. (2004). Studies toward the number of entries and time spent in open discovery of the next generation of antidepressants. 3. Dual 5-HT1A and serotonin transporter affinity within a class of N-aryloxyethylindolylalkylamines. J Med Chem. indicating its anti-anxiety effects in EPM Cremers, T.I. and Giorgetti, M. (2004) Inactivation of 5- in rats. Though escitalopram (0.5 mg/kg) HT(2C) receptors potentiates consequences of serotonin and alprazolam (0.25 mg/kg) increased reuptake blockade. Neuropsychopharmacology 29: 1782–1789. percentage preference to open arm entries,
both did not affected number of entries and
time spent in open arms. However,
addition of atenolol resulted in a
significant enhancement of anti-anxiety
effect, dose dependently. Our results are
in agreement with a large number of
literature reporting anti-anxiety effects of
β-blockers like atenolol, propranolol etc
(Durel et al., 1986; Hayes & Schulz,
1987). The results also justify the use of
combination of atenolol with alprazolam
(available in the market) and escitalopram
for anti-anxiety effects.
In the present study, the data clearly
demonstrates that chronic treatment with
atenolol produced antidepressant and
antianxiety effects on modified FST and
EPM respectively in rats. Its combination
with escitalopram also exhibited beneficial
effects. Hence, the study provided a
rationale for the co-administration of
atenolol with escitalopram, which may act
as a useful and potent combination in the
treatment of depressive disorders.
REFERENCE
Clerc, G.E. and Ruimy, P. (1995). A double blind comparison of venlafaxine and fluoxetine in patients hospitalized for major depression and melancholia. Intl Clin Psychopharmacol. 9:138 –143. Duman, R.S. and Charney, D.S (1999). Cell atrophy and loss in major depression. Biol Psychiatr.y 45:1083–1084.
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Moras09
Volumen 3, No. 1, 2009 Evaluación de un Sistema Inteligente de Semaforización Mediante Simulación para la Ciudad de Orizaba, Veracruz M.C. Constantino Gerardo Moras Sánchez Instituto Tecnológico de Orizaba [email protected] Departamento de Ingeniería Industrial Orizaba, Veracruz, México Ing. Juan Carlos Cortés Gutiérrez Instituto Tecnológico de Orizaba
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