Temelastine (also known as SK&F 93944) is a competitive histamine H1-receptor antagonist, which does not penetrate the central nervous system. This drug was studied as an anti-allergic agent. Experiments on animals have shown that the drug was efficacious vs. pharmacologic and antigen-induced bronchoconstriction.

Noberastine (NOB), a histamine H1 antagonist, has potent and specific peripheral antihistaminic activity. Noberastine, a furan derivative of nor-astemizole (an astemizole metabolite), has been shown to have a more rapid onset, and shorter duration of action than astemizole with peak antihistaminic activity at 4h following ingestion. Noberastine is rapidly absorbed and the peak plasma levels are obtained within 2 h of oral dosing. In preclinical studies Noberastine has been shown to lack central nervous system effects. After subacute (steady-state) administration of noberastine, there was increasing inhibition of weal and flare formation with higher doses of the drug. The 30 mg daily dose showed maximum antihistaminic effects.

Paquinimod is an immunomodulatory compound preventing S100A9 binding to TLR-4. It was studied in experimental osteoarthritis, in patients with mild active systemic lupus erythematosus and in systemic sclerosis patients. In January 2014, the US FDA granted orphan drug designation to paquinimod for the treatment of systemic scleroderma. The Orphan designation is implemented to promote the development of drugs that may provide significant benefit to patients suffering from rare diseases identified as life threatening or chronically debilitating. The further development of paquinimod for systemic lupus erythematosus and rheumatoid arthritis was discontinued.

Kythera Biopharmaceuticals (a subsidiary of Allergan) is developing setipiprant, an oral prostaglandin D2 (PGD2/CRTH2) receptor antagonist, for the treatment of alopecia. Setipiprant was initially developed as a treatment for allergic rhinitis, but recent hair loss-related discoveries have made it a better candidate for hair loss reversal. As CRTH2 antagonist, setipiprant, blocks the effects of prostaglandin D2 (PGD2) role in inflammation and, in consequence, the amplification and maintenance of allergic reactions. It targets the allergic inflammation at the beginning of the cascade. In clinical trials for allergic rhinitis and asthma, the drug performed quite well in the treatment of allergen-induced airway responses in asthmatic patients. It was also well tolerated by participants. However, its results were similar to those of drugs already on the market, so further trials were discontinued. In 2012, researchers discovered a link between the PGD2 receptor and hair loss. More specifically, this receptor is seen at high levels in the scalps of men diagnosed with Androgenetic Alopecia (AGA). setipiprant steps in before PGD2 attaches to the receptors, and therefore prevents receptor activation and, as a result, hair loss. With the discovery of the possible link to PGD2 receptors, Kythera acquired the drug, and trials began to test the effects of setipiprant on hair loss.

Napactadine is a bicyclic antidepressant agent. It is a histamine-H1 receptor antagonist. Preliminary results indicated a marked improvement in depressive symptomalology within 7 days of treatment, as measured by the Hamilton depression scale. However, clinical studies were discontinued after chronic administration of napactadine because an elevation in liver enzyme levels was observed in some patients.

Etolotifen is an antiasthmatic agent.

Dacemazine is a derivative of phenothiazine which acts as an antagonist of a histamine H1 receptor. The compound demonstrates local anesthetic activity and reduced the spasms produced by acetylcholine and histamine. In combination with di-tert-butylnaphthalenesulfonate, dacemazine was marketed under tradename Codopectyl as a spasmolytic and antitussive agent.

Perastine is an antihistaminic agent.

Eclazolast (REV 2871 or CHBZ) is a non-disodium cromoglycate (DSCG)-like, antiallergic drug. Eclazolast is taken up by rat mast cells and human leukocytes in a specific and saturable manner. The compound can be hydrolyzed by a granule-associated enzyme in the mast cell to an ionic metabolite (REV 3579) whose in vitro profile is identical to that of DSCG. Eclazolast is a potent inhibitor of both immunologic and non-immunologic histamine release. It inhibits exocytosis by intracellularly affecting only direct Fc(epsilon)RI linked processes and not through inhibition of Ca2+ influx channels.

Metoxepin was developed as an antiemetic, neuroleptic and antihistamine agent. This drug has never been marketed.