Iguratimod, a methanesulfonanilide, is an anti-inflammatory drug for the treatment of rheumatoid arthritis that has been developed exclusively in Japan and China. It inhibits the production of immunoglobulins and various inflammatory cytokines (interleukin-1, -6 and -8 and TNF), and exerts anabolic effects on bone metabolism by stimulating osteoblastic differentiation and inhibiting osteoclastogenesis. On the molecular level, it inhibits the nuclear transcription factor NF-κB but not its inhibitor, IκBα. In addition to these immunomodulatory and other long-lasting effects, iguratimod inhibits cyclooxygenase-2, which provides a synergistic short-term action against pain and inflammation. Efficacy and tolerability are comparable to salazosulfapyridine, and probably also to methotrexate. Combination with methotrexate is synergistic in patients with insufficient response to methotrexate and does not significantly increase adverse events.

Chloropyramine is an antagonist of H1 histamine receptors. It is indicated for the treatment of various forms of allergic reactions. Chloropyramine is a drug capable of (1) inhibiting the biochemical function of VEGFR-3 and FAK, (2) inhibiting proliferation of a diverse set of cancer cell types in vitro, and (3) reducing tumor growth in vivo.

Mebhydrolin (INN) or mebhydroline is a histamine H1-receptor antagonist. It is not available in the United States, but it is available in various other countries under the brand names Bexidal and Diazolin. It is used for symptomatic relief of allergic symptoms caused by histamine release, including nasal allergies and allergic dermatosis.

Thiazinamium is an anti-cholinergic phenothiazine deriva¬tive, which also has antihistaminic properties. Intramuscular injection of Thiazinamium induces considerable bronchodilatation, but inconsistent results have been obtained after oral administration. The bioavailability of oral Thiazinamium is only 2-3% of that occurring after intramuscular injection. Intrarectal Thiazinamium is slightly better absorbed (3-9%). The elimination half-life of the parenteral drug is short, being about 20 minutes in most patients. Thiazinamium has been available for the treatment of asthma since the early 1960s but currently withdrawn in most countries. Compared with inhaled ipratropium bromide, intramuscular Thiazinamium and intramuscular atropine were associated with 'extremely frequent side-effects’. Notable tachycardia occurred shortly after intramuscular injection of Thiazinamium in two trials. Dry mouth was reported as ‘frequent’ with oral Thiazinamium, and micturition problems of moderate severity affected 13% of patients.

Esonarimod (KE-298), a derivative of propionic acid developed in Japan, has been shown to suppress various animal models of arthritis by inhibiting the production of inflammatory cytokines, such as IL-1β, IL-6 and IL-8, from human peripheral blood mononuclear cells. In vitro, the two stereoisomers showed equivalent potency for antagonism of interleukin-1 and enhancement of lymphocyte transformation. Esonarimod also inhibited tumour necrosis factor-α-induced proliferation of synovial cells. Inhibition of proliferation of cells was not due to nonspecific cytotoxicity. Treatment with esonarimod also significantly reduced chloramphenicol acetyltransferase activity in synovial cells, and diminished activity of the transcription factor AP-1 in the nucleus of synovial fibroblast-like cells. In a phase II trial among 60 patients with rheumatoid arthritis, esonarimod 100-200 mg/day PO for 12 weeks produced significant improvements in the Lansbury index.

Talastine (trade name Ahanon), an alkylamine H1-antihistamine, was studied as a reason for an allergic drug exanthema.

TOLPROPAMINE is an alkylamine H1-antihistamine used as an antipruritic and topical antihistaminic.

Antihistamine agent

Platonin (4,4'-dimethyl-3,3'-di-n-heptyl-8-[2-(4-methyl-3-n-heptylthiazole)] -2,2'-dicarbocyanine diiodine) is one of the photosensitive trithiazolepentamethine cyanine dyes, with antioxidant, anti-inflammatory and anticancer activity. Platonin had also effects in rat models of endotoxemia which may have been mediated by a reduction of mean arterial blood pressure and inhibition of NO and free radical formation. Platonin inhibited the production of pyrogenic cytokines from human peripheral blood mononuclear cells (PBMC), resulting in antipyresis. Lipopolysaccharide (LPS) was shown to induce NF-kappaB activation of PBMC, and this effect was abolished by Platonin. Platonin is thus a potent macrophage-activating agent and immunomodulator. Platonin potently inhibited platelet aggregation and c-Jun NH2-terminal kinase (JNK) phosphorylation in collagen-activated platelets. The anti-aggregation effect did not affect bleeding time but increased occlusion time in platonin-treated mice. Platonin was potent in diminishing collagen- and Fenton reaction-induced ∙OH formation. Platonin exhibited remarkable neuroprotective properties against MCAO-induced ischemia in a mouse model through its antiaggregation, anti-inflammatory and antiradical properties.

Quifenadine is an antihistaminic agent. Quifenadine both blocks histamine H1-receptors in the peripheral tissues, and activates enzyme diaminoxidase (histaminase), due to this decreasing the histamine concentration in tissues. It is indicated in cases of pollinosis, acute and chronic urticaria, seasonal rhinitis (hay fever), allergic rhinitis, allergic conjunctivitis, angioneurotic Quinqe’s edema, dermatosis (eczema, neurodermatitis, pruritus etc.), allergic reactions caused by food or medicines. Quifanidine exhibits antiarrhythmic activity in children with frequent premature beats, without significant QT prolongation, or sinus node depression.