Fluoxetine causes decrease in intestinal motility

Background: Major depression is the most frequent disorder occurring in 16% of the population worldwide. In the middle of the 20th century, the discovery of selective serotonin (5-HT) reuptake inhibitors acted as a miracle in the antidepressant therapy. We explored the acute effects of fluoxetine and possible mechanism underlying the contractile effects of fluoxetine on isolated ileal smooth muscles of rabbit in vitro.Methods: Effects of increasing concentrations of acetylcholine (Ach), 5-HT and fluoxetine were studied on isolated ileal tissue of the rabbit in vitro by constructing cumulative concentration response curves. The ileal smooth muscle contractions were recorded on power lab (USA).Results: Ach, 5-HT and fluoxetine, produced a concentration-dependent reversible contraction of isolated ileal muscle of rabbit. The mean ± standard error of the mean of maximum amplitudes of contraction with Ach, 5-HT and fluoxetine, were 24.8±1.22 mm, 44±0.527 mm and 2.6±1.16 mm, respectively. Fluoxetine shifted the concentration-response curve right and downwards.Conclusion: Our study has indicated that fluoxetine on isolated ileal intestinal smooth muscle decrease the motility and this decrease in motility is possibly due to the inability of fluoxetine in vitro to enhance the serotonergic transmission and also because of the interaction of these agents with some of the other receptors, present in the intestinal smooth muscles

Insulin causes airway hyper-reactivity

Background: We explored the acute effects of insulin and one possible mechanism underlying the acute contractile effects of insulin on isolated tracheal smooth muscle of guinea pig in vitro.Methods: Effects of increasing concentrations of histamine (10−7-10−3 M), insulin (10−7-10−3 M), insulin pretreated with a fixed concentration of indomethacin (10−6 M) were studied on isolated tracheal tissue of guinea pig in vitro by constructing cumulative concentration response curves. The tracheal smooth muscle contractions were recorded with transducer on four channel oscillograph.Results: Histamine and insulin produced a concentration-dependent reversible contraction of isolated tracheal muscle of guinea pig. The mean±standard error of the mean of maximum amplitudes of contraction with histamine, insulin and insulin pretreated with indomethacin were 92.5±1.20 mm, 35±1.13 mm and 14.55±0.62 mm respectively. Indomethacin shifted the concentration-response curve of insulin to the right and downwards.Conclusions: Insulin has acute contractile effects on guinea pig airways, which were significantly inhibited by prostaglandin synthesis inhibitor indomethacin confirming the involvement of contractile prostaglandins in insulin-induced airway hyper-responsiveness

Effect of fluoxetine and paroxetine on intestinal motility

Background: Serotonin (5-HT) is a biogenic amine that functions as a neurotransmitter of sensorimotor functions in the digestive tract. Te role of 5-HT agents in the modulation of lower gastrointestinal function. Selective serotonin reuptake inhibitors (SSRIs) are of potential benefit in functional gastrointestinal diseases although formal evidence is lacking. Apart from central effects, they may have peripheral. The present study was carried out to find out the possible effects of fluoxetine and paroxetine on gastrointestinal smooth muscles of rabbit as they cause severe nausea and vomiting initially.Methods: Experimental study design. Power lab (USA) for recording the contractions of ileal smooth muscle of rabbit in response to serotonin, fluoxetine and paroxetine.Results: The percent responses with serotonin, fluoxetine and paroxetine were 100, 10.53, and 4.75 percent respectively.Conclusions: SSRIs (fluoxetine and paroxetine) were unable to enhance the serotonergic transmission in vitro inturn decreases the qualitative response

Early detection of doxorubicin-induced cardiotoxicity and its prevention by carvedilol

Background: The objective was to detect doxorubicin (Dox) - induced myocardial injury at early stage by quantitative estimation of cardio specific protein, cardiac troponin I (cTnI) and to explore the cardioprotective effects of carvedilol.Methods: The study design was lab-based randomized controlled in-vivo in rabbits conducted from January to August 2012. Cardiotoxicity was produced by single intravenous injection of 12 mg/kg body weight (BW) of Dox in a group of rabbits, control group was treated with normal saline only and the rabbits of third group were pre-treated with carvedilol 30 mg/kg of BW for 10 days before injecting Dox.Results: Dox induced cardiotoxicity was depicted by markedly raised serum levels of cTnI, creatine kinase-MB, lactate dehydrogenase, and Grade 3 necrosis of the heart tissue in rabbits. The pre-treatment with carvedilol resulted in improved serum levels of these biomarkers and the histological picture of heart tissue.Conclusions: Quantitative serum estimation of cTnI detects the presence of cardiotoxicity much before cardiac dysfunctions can be revealed by any other diagnostic technique. It can lead to significant economic impact in the management of cancer patients because the troponin-negative subjects can be excluded from long-term cardiac monitoring programs that involve high costs imaging techniques. The outcome of Dox chemotherapy can be made successful with the concurrent use of carvedilol

Inhibitory Effect of Sodium Cromoglycate on Insulin Induced Airway Hyper-Reactivity

Objective: To explore the acute effect of insulin on airway reactivity of guinea pigs and protective effects of sodium cromoglycate against insulin induced airway hyper-reactivity on isolated tracheal tissues of guinea pigs in vitro. Subjects and Methods: Effects of insulin (10-7- 10-3 M) and insulin pretreated with sodium cromoglycate (10-6 M) were observed on isolated tracheal strip of guinea pig (n=12) in vitro by constructing cumulative concentration response curves. The tracheal smooth muscle contractions were recorded with Transducer on Four Channel Oscillograph. Results: Insulin produced a concentration dependent reversible contraction of isolated tracheal muscle of guinea pig. The mean ± SEM of maximum amplitudes of contraction with insulin and insulin pretreated with sodium cromoglycate were 35 ± 1.13 mm and 14.55 ± 0.62 mm respectively. Cromoglycate shifted the concentration response curve of insulin to the right and downwards. Conclusion: Sodium cromoglycate significantly reduced the insulin mediated airway hyper-reactivity in guinea pigs. So we suggest that pretreatment of inhaled insulin with cromoglycate may have clinical implication in amelioration of its potential respiratory adverse effects such as bronchoconstriction

Preventive Effects of Ipratropium and Salbutamol Against Insulin Induced Tracheal Smooth Muscle Contraction in Guinea Pig Model: Ipratropium and Salbutamol inhibit Tracheal Contractions

Inhalational insulin was withdrawn from the market due to its potential to produce airway hyper-reactivity and bronchoconstriction. So, the present study was designed to explore the acute effects of insulin on airway reactivity of guinea pigs and protective effects of salbutamol and ipratropium against insulin induced airway hyper-responsiveness on isolated tracheal smooth muscle of guinea pig. The tracheal muscle contractions were recorded with transducer on four channel oscillograph. The mean ± SEM of maximum amplitude of contraction with increasing concentrations of insulin (10-7- 10-3 M), insulin pretreated with fixed concentration of salbutamol (10-7 M) and ipratropium (10-6 M) were 35 ± 1.13 mm, 14.55 ± 0.62 mm, and 27.8 ± 1.27 mm respectively. Salbutamol inhibited the contractile response of insulin greater than ipratropium on isolated tracheal muscle of guinea pig. So, we suggest that pretreatment of inhaled insulin with salbutamol may be preferred over ipratropium in amelioration of its potential respiratory adverse effects such as bronchoconstriction