Criteria used in this work to generate and select for new H1R antihistamine candidates were: i) search for higher H1R affinity children derived from second-generation antihistaminic parents / cavities by DWBEL co-evolution, ii) applying hundreds of non-toxic filters to reduce toxicities, iii) exclude crossdocking to other HRs (H1R 22 , H2R 17 , H3R 28 and H4R ), and iv) finetune predictions by additional filters for ADME properties such as brain-bloodbarrier, glycoprotein P brain efflux pumps , and P450 detoxification. Antihistaminic H1R candidates with reduced docking to H2R, H3R, H4R and Kv1.5 could be predicted among DWBEL generated top-children with drug-like properties, H1R sub-nanoMolar ADV affinities and low toxicities. Despite those predictions being highly hypothetical, some of these drug-like high-affinity small molecules specifically targeting H1R could add new tools to allergy basic research.