Effects of in vitro amitriptyline, fluoxetine, tranylcypromine and venlafaxine on saphenous vein grafts

Abstract Objective: In this study, we aimed to examine the effects of amitriptyline, fluoxetine, tranylcypromine and venlafaxine on saphenous vein grafts in coronary artery bypass graft surgeries. Methods: 59 patients (40 males and 19 females; mean age 65.1 years, distribution: 45-84 years) who had coronary artery bypass graft surgery between February 2014 and May 2016 were included in the study. After the saphenous vein grafts with intact and denuded endothelium were precontracted with 3×10-6M phenylephrine, amitriptyline, fluoxetine and tranylcypromine were cumulatively added to isolated organ baths in the range of 10-11-3x10-5M, while venlafaxine was added in the range of 10-9-3×10-5M. Then, the antidepressant-induced relaxation responses were recorded isometrically. Results: While the relaxation response of amitriptyline at -6.42 (Log M) was 74.6%, the response at -6.32 (Log M) was 75.5%. While the relaxation response at -6.46 (Log M) of fluoxetine was 68.02%, the response at -6.02 (Log M) was 72.12%. While the relaxation response of tranylcypromine at -7.53 (Log M) was 61.13%, the response at -7.23 (Log M) was 65.53%. While the relaxation response of venlafaxine at -6.21 (Log M) was 29.98%, the response at -5.90 (Log M) was 32.96%. Conclusion: The maximum relaxation at minimum and maximum therapeutic concentrations was obtained with amitriptyline, fluoxetine and tranylcypromine, and the minimum relaxation was obtained with venlafaxine. The relaxation responses were independent of the endothelium.

Amitriptyline, clomipramine, and maprotiline attenuate the inflammatory response by inhibiting neutrophil migration and mast cell degranulation

Objective: Despite the recognized anti-inflammatory potential of heterocyclic antidepressants, the mechanisms concerning their modulating effects are not completely known. Thus, we evaluated the anti-inflammatory effect of amitriptyline, clomipramine, and maprotiline and the possible modulating properties of these drugs on neutrophil migration and mast cell degranulation. Methods: The hind paw edema and air-pouch models of inflammation were used. Male Wistar rats were treated with saline, amitriptyline, clomipramine or maprotiline (10, 30, or 90 mg/kg, per os [p.o.]) 1 h before the injection of carrageenan (300 μg/0.1 mL/paw) or dextran (500 μg/0.1 mL/paw). Then, edema formation was measured hourly. Neutrophil migration to carrageenan (500 μg/pouch) and N-formyl-methionyl-leucyl-phenylalanine (fMLP) (10-6 M/mL/pouch) was also investigated in 6-day-old air-pouch cavities. Compound 48/80-induced mast cell degranulation was assessed in the mesenteric tissues of antidepressant-treated rats. Results: All tested antidepressants prevented both carrageenan- and dextran-induced edema. The anti-inflammatory effect of these drugs partially depends on the modulation of neutrophil migration, since they significantly counteracted the chemotactic response of both carrageenan and fMLP (p < 0.01). Furthermore, amitriptyline, clomipramine and maprotiline inhibited compound 48/80-induced mast cell degranulation (p < 0.001). Conclusions: These results suggest an important anti-inflammatory role of heterocyclic antidepressants, which is dependent on the modulation of neutrophil migration and mast cell stabilization. .

Antidepressant activity of fosinopril, ramipril and losartan, but not of lisinopril in depressive paradigms of albino rats and mice.

Fosinopril, ramipril and losartan significantly decreased the duration (sec) of immobility in forced swim test and were comparable to amitriptyline. The duration of immobility were significantly decreased in fosinopril, ramipril and losartan in the tail suspension test and were comparable to amitriptyline. Only losartan significantly increased the rearing number of entries, time spent (sec) in open arm and in light area in comparison to control animals. Fosinopril and ramipril and not lisinopril showed significant antidepressant activity while losartan showed a significant antidepressant and anxiolytic activity. Present findings suggest that these drugs could be better antihypertensives in hypertensive patients with comorbidity like depression or anxiety.

Antinociceptive effect of amitriptyline in mice of acute pain models.

Tricyclic antidepressant drugs induce antinociceptive effect and suggest that their analgesic action could be related to the monoaminergic activity of the drugs. The analgesic activity of amitriptyline was observed in mouse models of acute pain. Mice were divided into different groups and were given amitriptyline in different doses alone and in combination with morphine. Reaction time in Hot-Plate and Tail-Flick tests was observed. Results showed that amitriptyline had antinociceptive effect in acute pain state in experimental models. Amitriptyline in combination with morphine had better analgesic effect than the morphine alone in Hot-Plate test.

influence of different storage conditions on the stability of amitriptyline and fluphenazine in biological specimens

The aim of this research is to study the effect of different storage conditions [different temperatures and formalin preservation] on the stability of amitriptyline and fluphenazine in some biological samples. The LD[50] of amitriptyline and fluphenazine were administrated orally to rabbits which were sacrificed two hours after administration of the drugs. The tissues were stored at different conditions for six months. U.V. Spectrophotometer was used for estimation of the drugs at different periods. The results revealed that both amitriptyline and fluphenazine were rapidly declined in samples stored at room temperature [25 - 38°C]. It could not be detected in brain and liver samples at the end of three weeks, in the kidney at the end of four weeks and in plasma at the end of six weeks. While fluphenazine could not be detected in the brain at the end of three weeks, in the kidney and liver at the end of four weeks and in the plasma at the end of six weeks. At fridge temperature [5°C], amitriptyline could not be detected in brain and liver at the end of four weeks, in kidney samples at the end of six weeks. While fluphenazine could not be detected in brain at the end of four weeks, in kidney and liver at the end of six weeks, in plasma both of them couldn't be detected at the end of eight weeks. At freezer temperature [-20°C], amitriptyline could be detected up to the end of six months of the storage in the different samples with different relative recovery percent 80%, 75%, 69.57%, and 63.00% [for plasma, kidney, brain and liver samples respectively]. While fluphenazine could be detected up to the end four months of the storage in the plasma, kidney, and liver with different relative recovery percent [19.77%, 13.88%, and 11.56% respectively]. In brain fluphenazine could be detected up to the end of twelve weeks with a relative recovery percent of 15.76%. In samples preserved in 10% formalin solution, amitriptyline could be detected up to the end of six months of the storage in the different samples with high relative recovery percents [90.81%, 90.18%, 87.84% and 86.14%] for the kidney, plasma, brain, and liver respectively. While fluphenazine could not be detected in brain samples at the end of six weeks. It could not be detected in liver, kidney, and plasma at the end of eight weeks of the storage. In conclusion amitriptyline is stable in tissues stored at freezer [-20°C] and that preserved in formalin solution. While fluphenazine is stable in tissues stored at freezer [-20°C] for sometime, but it is not stable in the samples stored at room temperature, fridge temperature, and in samples preserved in formalin solution

Thyroid function in depression.

Studies on thyroid functions were performed on patients suffering from depression. Thirty four cases of depression were studied for their thyroid function and showed a diminished level of T3 and T4 with concomitant rise in TSH (Thyroid Stimulating Hormone) level. This work showed that depressive patients had been suffering from sub-hypothyroidism.

Influence of antidepressant drugs on learning and memory paradigms in mice.

Effect of antidepressant drugs (amitriptyline, imipramine and fluoxetine) on cognitive functions, impaired by the muscarinic antagonist scopolamine were investigated in mice. The changes in learning and memory tasks were studied using transfer latency on elevated plus maze and employing number of descents in passive avoidance paradigms. Amitriptyline and imipramine showed significant memory impairment. They also potentiated scopolamine-induced memory deficit in a significant way. Amitriptyline and imipramine impair cognitive function possibly due to their anticholinergic properties. Fluoxetine, a newer antidepressant, however showed no effect on learning and memory. It significantly reversed the scopolamine-induced memory impairment in both the tests. Fluoxetine with no anticholinergic property may prove to be a better drug in endogenous depression in elderly patients.

Effect of amitriptyline on blood glucose level in rabbits.

Effect of single graded doses of amitriptyline (4, 8 and 16, mg/kg, p.o.) were observed on blood glucose level in 18 h fasted albino rabbits. All the doses of Amitriptyline produced significant hyperglycemia at 4 h, which attained a peak at 24 h with 16 mg/kg dose and appears to be due to blockade of the uptake of monominergic transmitters across the axoplasmic membrane, It (16 mg/kg) also produced glucose intolerance during early hours probably due to interference with gastrin function.

Effect of amitriptyline on histamine and bethanechol-stimulated gastric secretion in male rats

Amitriptyline, a tricyclic anti-depressant, was tested for its antimuscarinic and antihistaminic effects against bethanechol and histamine-stimulated gastric secretion in male rats. Daily intramuscular injection of Amitriptyline [5 mg/kg body weight] for two weeks proved to be effective only in inhibiting bethanechol-stimulated gastric secretion. Amitriptyline produced a significant reduction in both free and total acidity of the gastric juice, with significant increase in mucin content, but no change in its peptic activity. The role of Amitriptyline in blocking Bethanechol-stimulated gastric secretion may suggest that the ulcer healing is caused by its anticholinergic activity

Effect of amitriptyline on blood glycose, insulin, lipids, thyroid function, electrolytes and some brain amino acids in rabbits

The intraperitoneal administration of amitriptyline [10 mg/kg body weight for 14 days] resulted in a significant decrease in blood glucose, significant increase in the blood insulin level, significant decrease in the levels of free fatty acids [FFA], triglycerides and total cholesterol. It also produced a significant decrease in both sodium and potassium levels and an increase in brain GABA level. However, T3, T4, TSH and brain L-glutamic acid showed no change. The probable significance of the findings is discussed