Article

Evaluation of anti-inflammatory activity, effect on blood pressure & gastric tolerability of antidepressants

Department of Pharmacology, Maulana Azad Medical College, New Delhi, India.
The Indian Journal of Medical Research (Impact Factor: 1.66). 07/2013; 138(1):99-103.
Source: PubMed

ABSTRACT Background & objectives:
Antidepressants are being used as analgesics for various pain related disorders like neuropathic and non neuropathic pain. Although their analgesic activity is well recognized but anti-inflammatory potential of antidepressants is still inconclusive. Since the antidepressants are used for longer duration, it becomes important to elucidate effect of anti-depressants on blood pressure and gastric mucosa. This study was undertaken to evaluate the anti-inflammatory potential of various antidepressant drugs as well as their effect on blood pressure and gastric tolerability on chronic administration in rats.

Methods:
Rat paw oedema model was used for studying anti-inflammatory activity, single dose of test drug (venlafaxine 20 and 40 mg/kg, amitryptline 25 mg/kg, fluoxetine 20 mg/kg) was administered intraperitoneally 45 min prior to administration of 0.1 ml of 1 per cent carrageenan in sub-planter region. Oedema induced in test group was compared with normal saline treated control group. For studying effect on blood pressure and gastric tolerability, test drugs were administered for 14 days. Blood pressure was recorded on days 0, 7 and 14 using tail cuff method. On day 14, 4 h after drug administration, rats were sacrificed and stomach mucosa was examined for ulcerations.

Results:
Pretreatment of rats with venlafaxine (40 mg/kg) resulted in a significant decrease in paw oedema as compared to control (2.4 ± 0.15 to 1.1 ± 0.16 ml, P<0.01). Similarly, in the group pretreated with fluoxetine, significant decrease in paw oedema was observed in comparison to control (P<0.05). Significant change in mean blood pressure was seen in rats pretreated with venlafaxine 40 mg/kg (126.7 ± 4.2 to 155.2 ± 9.7, P<0.05) and fluoxetine (143.5 ± 2.6 to 158.3 ± 1.2, P<0.05) on day 7. No significant difference with regard to gastric tolerability was observed among groups.

Interpretation & conclusions:
Our findings showed significant anti-inflammatory activity of venlafaxine (40 mg/kg) and fluoxetine but these drugs were also associated with an increase in blood pressure. No significant change in mean ulcer index was observed among groups.

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    ABSTRACT: Hypertensive encephalopathy with the clinicoradiological entity posterior reversible encephalopathy syndrome in the setting of venlafaxine as single therapy has not been reported earlier. A 46-year-old man developed hypertensive encephalopathy associated with venlafaxine as single therapy. Magnetic resonance imaging of the brain, pre and post gadolinium, carried out on day 2, displayed an increased T2 signal in the cortex on both the T2 and FLAIR images throughout the frontal and temporal lobes and in the cerebellum. Venlafaxine therapy was stopped. The patient gradually improved and he became seizure free and the blood pressure successively became normal. A magnetic resonance imaging after six weeks displayed marked regression of the abnormalities. On follow-up after 3 months, his blood pressure had been normal and he had not had any symptoms. The prescribed antiepileptic drug was discontinued as well as antihypertensive treatment. He had not experienced any new symptoms at follow-up after one year. The patient in this report had hypertensive encephalopathy associated with venlafaxine therapy. The imaging findings are compatible with hypertensive encephalopathy/posterior reversible encephalopathy syndrome. Venlafaxine is a drug used very frequently. Venlafaxine may infrequently induce hypertensive crisis. Hypertensive encephalopathy may rarely occur in the setting of venlafaxine as single therapy even in low to moderate doses. Patients on venlafaxine should have regular monitoring of blood pressure. Knowledge of the side effects is vital. Venlafaxine must be discontinued if significant hypertension persists.
    SpringerPlus 12/2015; 4(1):97. DOI:10.1186/s40064-015-0883-0