Rupatadine (UR-12592) is a potent dual PAF H1 antagonist with Ki of 0.55 0.1 uM(rabbit platelet membranes guinea pig cerebellum membranes).IC50 value:Target: PAF H1 antagonistin vitro: Rupatadine competitively inhibited histamine-induced guinea pig ileum contraction (pA2 = 9.29 + - 0.06) without affecting contraction induced by ACh, serotonin or leukotriene D4 (LTD4). It also competitively inhibited PAF-induced platelet aggregation in washed rabbit platelets (WRP) (pA2 = 6.68 + - 0.08) and in human platelet-rich plasma (HPRP) (IC50 = 0.68 microM), while not affecting ADP- or arachidonic acid-induced platelet aggregation [1]. The IC50 for rupatadine in A23187, concanavalin A and anti-IgE induced histamine release was 0.7+ -0.4 microM, 3.2+ -0.7 microM and 1.5+ -0.4 microM, respectively whereas for loratadine the IC50 was 2.1+ -0.9 microM, 4.0+ -1.3 M and 1.7+ -0.5 microM. SR-27417A exhibited no inhibitory effect [2].in vivo: Rupatadine blocked histamine- and PAF-induced effects in vivo, such as hypotension in rats (ID50 = 1.4 and 0.44 mg kg i.v., respectively) and bronchoconstriction in guineapigs (ID50 = 113 and 9.6 micrograms kg i.v.). Moreover, it potently inhibited PAF-induced mortality in mice (ID50 = 0.31 and 3.0 mg kg i.v. and p.o., respectively) and endotoxin-induced mortality in mice and rats (ID50 = 1.6 and 0.66 mg kg i.v.) [1]. rupatadine treatment improved the declined lung function and significantly decreased animal death. Moreover, rupatadine was able not only to attenuate silica-induced silicosis but also to produce a superior therapeutic efficacy compared to pirfenidone, histamine H1 antagonist loratadine, or PAF antagonist CV-3988 [3]. [1]. Merlos M, et al. Rupatadine, a new potent, orally active dual antagonist of histamine and platelet-activating factor (PAF). J Pharmacol Exp Ther. 1997 Jan;280(1):114-21. [2]. Queralt M, et al. In vitro inhibitory effect of rupatadine on histamine and TNF-alpha release from dispersed canine skin mast cells and the human mast cell line HMC-1. Inflamm Res. 2000 Jul;49(7):355-60. [3]. Lv XX, et al. Rupatadine protects against pulmonary fibrosis by attenuating PAF-mediated senescence in rodents. PLoS One. 2013 Jul 15;8(7):e68631.
Luvangetin may have anti-inflammatory activity, it can inhibit NO and PGE2 production in LPS-stimulated BV2 cells. Luvangetin shows significant protection against pylorus-ligated and aspirin-induced gastric ulcers in rats and cold restraint stress-induced
11-deoxy PGF1α is a synthetic analog of PGF1α. In whole animal studies, a dose of 32 mg kg inhibited gastric acid secretion by 35%. 11-deoxy PGF1α is also known to cause rat uterine contractions at a dose 0.3 times that of PGF1α. It also exhibits vasopressor and bronchoconstrictor activities at about half the potency of PGF2α in guineapigs.
Lincydomine is a smooth muscle relaxant, beneficial to the treatment of unstable angina pectoris, but also can open the respiratory tract of humans and guineapigs.
Mabuterol, (S)- is a D isoform of Mabuterol, which is a selective β2 adrenoreceptor agonist. Mabuterol has been found to decrease the blood pressure in rats and increase heart rate and contractile force in guineapigs. Mabuterol inhibited the positive inotropic effect of isoprenaline but has no effect on alpha-adrenergic, acetylcholine and histamine receptors.
Methoctramine is a selective antagonist of M2 muscarinic acetylcholine receptors (IC50 = 6.1 nM in CHO-K1 cell membranes).[1] It is selective for M2 over M1, M3, M4, and M5 receptors (IC50s = 92, 770, 260, and 217 nM, respectively). In vitro, methoctramine inhibits acetylcholine-induced reductions in isolated guinea pig tracheal tube contractions when used at a concentration of 1 μM.[2] In vivo, methoctramine inhibits bradycardia and bronchoconstriction induced by acetylcholinein guineapigs with ED50 values of 38 and 81 nmol kg, respectively. In a rat model of spinal cord injury, methoctramine suppresses bladder overactivity induced by the non-selective muscarinic acetylcholine receptor agonist oxotremorine M.[3]
Prostaglandin F2β (PGF2β) is the 9β-hydroxy stereoisomer of PGF2α. It is much less active than PGF2α in antifertility and bronchoconstrictor activities. PGF2β exhibits bronchodilating activity in guineapigs and cats and antagonizes the bronchoconstrictor activity of PGF2α.