International Journal of Technical Research(IJTR) Vol. 2, Issue 1, Mar-Apr 2013 ABSTRACT DRUG PROFILE 1. Escitalopram
escitalopram is 10 mg once daily for the
combination of two drugs i.e. atenolol and
continue or if side effects occur during the
escitalopram were taken and by using the
dosage. Escitalopram may be taken with or
dose of drugs was compared to the control
without food, but should be taken at the
significant as compared to control value of
observe the anti anxiety of drug on the rats
vehicle treated to time spent in open arm of
The term "major depressive disorder" was
atenolol does not pass through the blood-
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
al.,1985) for studying the anxiolytic effect
in rodents was used. EPM consists of two
disorder in clinical and research use. Major
depression is a disabling condition which
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
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:
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:
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 International Journal of Technical Research(IJTR) Vol. 2, Issue 1, Mar-Apr 2013
F= 6.38, p=0.008* compare to respective vehicle control group
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
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
observe the effects of SSRIs in rats also
provides a unique tool to understand the
swimming significantly. Escitalopram is S-
enantiomer of citalopram which is reported
(Maciej et al., 2007; Cryan et al., 2002;
to increase swimming behavior at the cost
of climbing and immobility (Maciej et al.,
neurons on mobility of rats in FST is well
established (West, 1990; Aghajanian et al.,
1997; Klimek et al., 1997). An increase in
significantly. The mechanism involved is
increase in 5-HT synaptic concentration,
reduction in the activity has the opposite
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
[III] Frodl, T. and Meisenzahl, E.M. (2003). Larger amygdala
volumes in first depressive episode as compared to
recurrent major depression and healthy control subjects.
individual administration of these drugs on
[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.
[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.
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.
[VIII] Blier, P. and Bergeron, R. (1998). The use of pindolol to
potentiate antidepressant medication. J Clin Psychiatry. 59:16 -23.
[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
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
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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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Working Guidelines Sarah MATHESON and John OSHA, Deputy Reporters General Anne Marie VERSCHUR, Sara ULFSDOTTER and Kazuhiko YOSHIDA Second medical use and other second indication claims Introduction This question seeks to determine the type, scope and enforcement of patent protection for new uses of known chemical compounds when a known substance is found to have a new therapeutic