Date of Award

11-2015

Document Type

Thesis

Degree Name

Master of Science in Medical Sciences (MSMS)

Department

Medical Education

First Advisor

Dr. Murat Oz

Second Advisor

Dr. Chris Howarth

Third Advisor

Dr. Bassem Sadek

Abstract

Thujone is a natural compound found in plants such as “wormwood” and “sage” and it’s also found in the alcoholic drink “Absinthe”. Thujone has been suggested as a neurotoxic compound and reported to modulate GABAA receptors. In this study, we investigated the pharmacology of Thujone on nicotinic receptors expressed in Xenopus oocytes using the two electrode voltage clamp method. Thujone (100μM) caused an 80% inhibition of Acetylcholine (ACh) induced currents in human α7-nAChRs expressed in frog oocytes while only 30% inhibition currents in α4β2 expressed oocytes and no effect on α3β4, α3β2 and α4β4 nAChRs. The mechanisms of Thujone effect on the α7-nAChR were further investigated and found to be independent of membrane potential and did not compete with ACh. Furthermore, Thujone did not affect the activity of endogenous Ca2+ dependent Cl- channels. In conclusion, Thujone inhibits human nAChRs with different potencies

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