<P> The vast majority of marketed H - antihistamines are receptor antagonists and only a minority of marketed compounds are inverse agonists at the receptor . Clinically, H - antihistamines are used to treat allergic reactions and mast cell - related disorders . Sedation is a common side effect of H - antihistamines that readily cross the blood--brain barrier; some of these drugs, such as diphenhydramine and doxylamine, are therefore used to treat insomnia . H - antihistamines can also reduce inflammation, since the expression of NF - κB, the transcription factor the regulates inflammatory processes, is promoted by both the receptor's constitutive activity and agonist (i.e., histamine) binding at the H receptor . </P> <P> A combination of these effects, and in some cases metabolic ones as well, lead to most first - generation antihistamines having analgesic - sparing (potentiating) effects on opioid analgesics and to some extent with non-opioid ones as well . The most commonly used for the purpose include hydroxyzine, promethazine (enzyme induction especially helps with codeine and similar prodrug opioids), phenyltoloxamine, orphenadrine, and tripelennamine; some may also have intrinsic analgesic properties of their own, orphenadrine being an example . </P> <P> Second - generation antihistamines cross the blood--brain barrier to a much lower degree than the first - generation antihistamines . Their main benefit is they primarily affect peripheral histamine receptors and therefore are less sedating . However, high doses can still induce drowsiness through acting on the central nervous system . Some second - generation antihistamines, notably cetirizine, can interact with CNS psychoactive drugs such as bupropion and benzodiazepines . </P> <P> Examples of H antagonists include: </P>

Do second generation antihistamines cross the blood brain barrier