ReN 1869 hydrochloride is a novel, selective antagonist of histamine H1 receptor.

H1 receptor:ki:0.19±0.04 μM

ReN 1869 is a highly selective tricyclic antihistamine that shows functional histamine H1 receptor antagonism.?ReN 1869 is profiled for activity at 10 μM at various receptors, transporters, enzymes and ion channels.?ReN 1869 only demonstrates affinity to the histamine H1 receptor (guinea pig brain, [3H]pyrilamine) with a Ki of 0.19±0.04 μM and the non-selective σ site [guinea pig brain, [3H]1,3-di-tolylguanidine (DTG)] with a Ki of 0.45 μM.?ReN 1869 dose-dependently reduces the responses with IC50 of 1.70±0.002 μM.

ReN 1869 is a novel, selective histamine H(1) receptor antagonist.?It is orally available, well tolerated, easily enters the central nervous system (CNS) but no adverse effects are seen in mice at 300 mg/kg.?ReN 1869 at 0.01-10 mg/kg is antinociceptive in tests of chemical nociception in rodents (formalin, capsaicin, phenyl quinone writhing) but not in thermal tests (hot plate and tail flick).?ReN 1869 amplifies the analgesic action of morphine but does not show tolerance after chronic dosing.?Moreover, the compound is effective against inflammation of neurogenic origin (antidromic nerve stimulation, histamine-evoked edema) but not in carrageenan-induced inflammation.?We suggest that ReN 1869, via H(1) blockade, counteracts the effect of histamine liberated from activated mast cells and inhibits pain transmission in the dorsal spinal cord.?ReN 1869 represents a new class of antihistamines with pain-relieving properties that probably is mediated centrally through histamine H(1) receptors but alternative mechanisms of action cannot be excluded.