4.6 Article

Repurposing of Iloperidone: Antihypertensive and ocular hypotensive activity in animals

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DOI: 10.1016/j.ejps.2019.105173

Keywords

Iloperidone; Hypotension; Antihypertensive; Ocular hypotensive; Drug repurposing

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Purpose: Iloperidone, second generation antipsychotic drug, reported in clinical trial to produce orthostatic hypotension as side effect. It was claimed to be antagonistic at alpha adrenergic receptor in central nervous system. We evaluated effect of Iloperidone on peripheral alpha 1 adrenoreceptor by in silico and in vitro methods while in vivo hypotensive, antihypertensive and ocular hypotensive activity was evaluated in animals. Methods: Pharmacological activity prediction of Iloperidone was done using PASSOnline and SwissTargetPrediction softwares and molecular docking with Alpha 1A adrenoreceptor using AutoDock Vina. Hypotensive activity in normotensive and antihypertensive activity against DOCA-salt induced hypertension in rats were evaluated at doses 0.03 mg/Kg and 0.1 mg/Kg, i.p of Iloperidone. Blood pressure was measured by invasive blood pressure measurement technique using PowerLab 4/30 and intraocular pressure was measured using digital tonometer. Results: Iloperidone (0.1 mg/Kg) showed significant decrease in blood pressure (38.96 +/- 1.1%) in normotensive rats, while in DOCA salt induced hypertensive rats, systolic blood pressure was found to be decreased by 29.04 +/- 1.45% and 31.43 +/- 1.21% in 0.03 mg/Kg and 0.1 mg/Kg treated rats respectively. Iloperidone prevented rise in systolic BP with adrenaline. Intraocular pressure was found to be decreased by 36.66 +/- 3.15% in rabbits after 1 h of instillation of 0.1% Iloperidone. Conclusion: Iloperidone exerted hypotensive and/or anti-hypertensive activity in rats and ocular hypotensive activity in rabbits.

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