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R-(-)-α-Methylhistamine is a histamine H3 receptor agonist with diverse biological activities. It inhibits the release of histamine induced by antidromic electrical stimulation of the sciatic nerve in rats when administered at doses ranging from 0.25 to 2 mg/kg, an effect that can be reversed by the selective histamine H3 receptor antagonist thioperamide . R-(-)-α-Methylhistamine (0.5-50 nmol) inhibits gastric acid secretion in rats when administered intracerebroventricularly but not intravenously. It reduces isolation-induced vocalizations and aggressive behavior in a resident-intruder test in guinea pig pups and mice, respectively. R-(-)-α-Methylhistamine (30 mg/kg) decreases freezing time in a conditioned fear stress test in rats. It also acts synergistically with fentanyl to reduce nociception and plasma extravasation in a mouse model of chronic inflammation induced by complete Freund's adjuvant.

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