Imetit and N-methyl derivatives. The transition from potent agonist to antagonist at histamine H3 receptors.1

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Abstract

Imetit {S-[2-(imidazol-4-yl)ethyl]isothiourea} is a potent H3-agonist in vitro (on rat brain cortical slices; EC50 = 1 nM) and in vivo (ED50 ∼ 1 mg/kg per os in mice). N-Methylimetit is also an agonist (EC50 = 15 nM) but dimethyl and trimethyl derivatives are antagonists (Ki = 50 - 500 nM).

Imetit {S-[2(imidazol-4-yl)ethyl]isothiourea} (R1 = R2 = R3 = H) is a potent H3-agonist in vitro (on rat brain cortical slices; EC50 = 1 nM) and in vivo (ED50 ∼ 1 mg/kg per os in mice). N-Methylimetit is also an agonist (EC50 = 15 nM) but dimethyl and trimethyl derivatives are antagonists (Ki = 50 - 500 nM).

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