DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20200719

Evaluation of antidepressant effect of angiotensin receptor blocker telmisartan in albino mice

Keerthana Brattiya, Malar Sivaraman

Abstract


Background: Depression and hypertension are common morbidities which are seen in elderly and also one leads to the other. Present antidepressant drugs are known for its side effects and there is a necessary for newer drugs with lesser adverse effects. Telmisartan being a widely used antihypertensive drug and with multiple additional properties like peroxisome proliferator-activated receptor gamma activity along with blunting of renin-angiotensin-aldosterone system can be a potential drug for depression. Hence this study is aimed to evaluate the antidepressant activity of angiotensin receptor blocker telmisartan in animal models.

Methods: As per protocol submitted to ethics committee, 24 male albino mice weighing between 20-30grams of either sex were selected and divided into 4 groups consisting of 6 each. They were housed in cages with food and water ad libitum. Animals were kept in ambient temperature and humidity, with a 12-hour light and 12-hour dark cycle.  Group 1 and group 2 were administered distilled water and fluoxetine 10 mg/kg respectively only on day 15, whereas group 3 and group 4 received telmisartan per orally 1 mg/kg and 2 mg/kg respectively for 15 days once daily. All animals were tested on day 15 using tail suspension test for antidepressant effect.

Results: There was significant reduction in the immobility time in telmisartan group when compared to the control group and this time was comparable with the immobility time of standard drug fluoxetine. Decrease in immobility time was found to statistically significant by using one-way ANOVA followed by Bonferroni post hoc test.

Conclusions: As evident from our study, telmisartan can be a newer target for antidepressant effect.


Keywords


Telmisartan, Antidepressant, Peroxisome proliferator-activated receptor gamma

Full Text:

PDF

References


Hasler G. Pathophysiology of depression: do we have any solid evidence of interest to clinicians? World Psychiatr. 2010;9(3):155-61.

Simonsick EM, Wallace RB, Blazer DG, Berkman LF. Depressive symptomatology and hypertension-associated morbidity and mortality in older adults. Psychosom Med. 1995;57(5):427-35.

Wright JW, Yamamoto BJ, Harding JW. Angiotensin receptor subtype mediated physiologies and behaviors: New discoveries and clinical targets. Prog Neurobiol. 2008;84(2):157-81.

Guimond MO, Payet NG. “The Angiotensin II Type 2 Receptor in Brain Functions: An Update. Inter J Hypertens. 2012;2012.

Steru L, Chermat R, Thierry B, Simon P. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacol. 1985;85(3):367-70.

Noda A, Fushiki H, Murakami Y, Sasaki H, Miyoshi S, Kakuta H, Nishimura S. Brain penetration of telmisartan, a unique centrally acting angiotensin II type 1 receptor blocker, studied by PET in conscious rhesus macaques. Nuclear Med Biol. 2012;39(8):1232-5.

Wang JM, Tan J, Leenen FH. Central nervous system blockade by peripheral administration of AT1 receptor blockers. J Cardiovasc Pharmacol. 2003;41:593-9.

Nayak V, Patil PA. Antidepressant activity of fosinopril, ramipril and losartan, but not of lisinopril in depressive paradigms of albino rats and mice. Ind J Experiment Biol. 2008;46(3):180-4.

Kasahara Y, Taguchi A, Uno H, Nakano A, Nakagomi T, Hirose H, et al. Telmisartan suppresses cerebral injury in a murine model of transient focal ischemia. Brain Res. 2010;1340:70-80.

Kobayashi T, Kawamata T, Shibata N, Okada Y, Kobayashi M, Hori T. Angiotensin II type 1 receptor blocker telmisartan reduces cerebral infarct volume and peri-infarct cytosolic phospholipase A2 level in experimental stroke. J Neurotr. 2009;26(12):2355-64.

Li Y, Cheng KC, Liu KF, Peng WH, Cheng JT, Niu HS. Telmisartan activates PPARδ to improve symptoms of unpredictable chronic mild stress-induced depression in mice. Scientific Reports. 2017;7(1):1-1.

Wang J, Pang T, Hafko R, Benicky J, Sanchez-Lemus E, Saavedra JM. Telmisartan ameliorates glutamate-induced neurotoxicity: roles of AT (1) receptor blockade and PPARgamma activation. Neuropharmacol. 2014;79:249-61.

Saavedra JM. Angiotensin II AT (1) receptor blockers as treatments for inflammatory brain disorders. Clin Sci (Lond). 2012;123:567-90.