Locomotor differences in Mongolian gerbils with the effects of midazolam administration in the form of eye drops

Akcan Akkaya, Umit Y Tekelioglu, Abdullah Demirhan, Mesut Erdurmus, Tayfun Apuhan, Hakan Bayir, Erol Ayaz, Hasan Kocoglu

Abstract

Background: Midazolam is a sedative-hypnotic agent with amnestic and anticonvulsant properties that can be administrated to mammals through various routes, such as intravenous, intramuscular, oral, intrathecal, rectal, and buccal. Midazolam administration in the form of eye drops through the conjunctiva is not reported in the literature. Aim:This study aims to demonstrate the possible central nervous system effects of midazolam administration as eyes drops in Mongolian gerbils. Materials and Methods: Fourteen gerbils were randomly assigned to one of two equal sized groups. The active arm received 2 ml of 10 mg midazolam as eye drops in both eyes. Control group received a total of 2 ml of physiological saline(0.9% NaCl). We subjected the gerbils to an adapted “Open Field” to determine the possible effects on central nervous system of midazolam. Gerbils were allowed to move freely in the open field. Before and after the drug administration, locomotor activities of each gerbil have been recorded. Frequency of loss of righting reflex was quantified. Results: Conjunctival Midazolam administration resulted with the transient loss of righting reflex (p=0.017) and suppressed exploration motion (p=0.018) in the open field test compared to control subjects. Conclusions: In the present study, administration of conjunctival midazolam as an eye drop may affect gerbil’s locomotor activities and open field behaviors. We argue that, using a sedative and anticonvulsive drug such as midazolam via conjunctival route may be useful in some clinical situations. Therefore, it could be beneficial to develop a new conjunctival formulation of midazolam. Also, there is a need for trials in humans with pharmacokinetic studies.

Keywords: Righting reflex; Conjunctival Midazolam; Gerbillinae; Midazolam; Eye drop; New administration route

African Health sciences Vol 14 No. 1 March 2014