Interaction with Histamine H₁-Receptors and Bronchospasmolytic Effects of Urapidil

Abstract

The antihypertensive drug, urapidil, competitively antagonized the hista-mine-induced contractions in guinea pig isolated tracheal and ileal preparations. Its affinity to histamine H₁-receptors was 3-fold higher than that of histamine but 10- and 30-fold weaker than that of diphenhydramine and indoramin, respectively. Urapidil did not inhibit contractions induced by muscarinic agonists in both organs. Investigations in spontaneously breathing guinea pigs showed a greater efficacy of urapidil than that of diphenhydramine in protecting the animals against histamine-induced bronchospasms, whereas acetylcholine-induced spasms were only moderately inhibited. The-ophylline, at a 100-fold higher dosage than urapidil, protected the animals against both histamine and acetylcholine challenges. This experimentally observed effect of urapidil supports clinical trials in hypertensive patients suffering also from obstructive lung disease and/or allergic illness.

In vitro and in vivo uroselectivity of B8805-033, an antagonist with high affinity at prostatic α 1A - vs. α 1B - and α 1D -adrenoceptors

“…In guinea pig ileum, histamine concentration-response curves were shifted to the right in a parallel fashion by B8805-033 (3×10 -7 -3×10 -5 M), indicating competitive antagonism at histamine H 1 -receptors with a pA 2 value of 6.74±0.06 (slope 0.92±0.10; means ± SEM, n=12; not shown), the value of which is also nearly identical to that determined previously for urapidil (pA 2 6.81; Kilian et al 1987). Similarly, 5-methyl-urapidil (3×10 -7 -10 -5 M) and flesinoxan (10 -6 -10 -5 M) competitively antagonized histamine-induced contraction in this tissue and pA 2 values were 6.48±0.06 (slope 0.89±0.07) and 5.95±0.07 (slope 0.90±0.05), respectively (Table 1).…”