The Mode of Action Of 5-Hydroxytryptamine

Abstract

1. The isolated salivary gland of the blowfly Calliphora has been used to study the molecular pharmacology of 5-hydroxytryptamine (5-HT). 2. Ethylamine alone is inactive but the addition of extra carbon atoms or ring systems (imidazole or benzene) introduces some activity. A 5-hydroxyindole ring confers most activity. 3. If the hydroxyl group is either removed, replaced with other groups, or displaced to the 4- or 6-position on the indole ring there is a large reduction in activity. 4. The activity of the molecule is greatly reduced if the length of the side chain is decreased (gramine) or increased (3-aminopropyl indole) by a single carbon atom. Such molecules are effective competitors. 5. These structure-activity studies suggest that the specificity of 5-HT resides in the 5-hydroxyindole moiety which binds the molecule to the receptor while the positively charged ethylamine side chain is responsible for inducing the hormonal effect.