An old antihistamine¹ was used as the blueprint for development of the first commercialized SSRI. Similar first generation antihistamines² also have a significa

An old antihistamine¹ was used as the blueprint for development of the first commercialized SSRI. Similar first generation antihistamines² also have a significant effect on SERT (serotonin transporter). Reciprocly, the weight gain induced by certain SSRI is tought to be caused by an antihistaminic effect³. It would not be surprising if other antihistamines (at least those that cross the BBB) had similar effects because antihistamines are frequently promiscuous (i.e. they have significant affinities with a lots of targets other than the one that make a drug effective) but I would be surprised if histamine, or its inhibition, was directly (with the exclusion of the miserable feeling that comes with allergies) implicated in moods changes. 1- https://en.wikipedia.org/wiki/Brompheniramine https://en.wikipedia.org/wiki/Brompheniramine 2- https://en.wikipedia.org/wiki/Chlorphenamine https://en.wikipedia.org/wiki/Chlorphenamine 3- https://pubmed.ncbi.nlm.nih.gov/27593622 https://pubmed.ncbi.nlm.nih.gov/27593622