Thioperamide is a potent HRH₄ antagonist and selective HRH₃ antagonist capable of crossing the blood–brain barrier. It was used by Jean-Charles Schwartz in his early experiments regarding the H₃ receptor. Thioperamide was found to be an antagonist of histamine autoreceptors, which negatively regulate the release of histamine. The drug enhances the activity of histaminergic neurons by blocking autoreceptors, leading to greater release of histamine.

Its action on H₃ receptors is thought to promote wakefulness and improve memory consolidation.