In:
Drug Development Research, Wiley, Vol. 8, No. 1-4 ( 1986-05), p. 187-195
Abstract:
The effect of ritanserin was determined on a variety of isolated smooth muscle tissues. The compound is a potent antagonist of serotonin‐induced contractions of isolated blood vessels (IC50‐, A h ‐ or A 2 −value between 5.6 × 10 −11 and 3.3 × 10 −10 M) and trachea (IC50 = 1.6 × 10 −8 M) and of serotonin−induced bronchospasms in anaesthetised guineapigs (ED50 = 0.026 mg/kg i.p.). In most tests ritanserin was more potent than ketanserin (IC50‐ or A 2 ‐value between 5.1 × 10 −10 and 2.6 × 10 −9 M) as a serotonergic antagonist. In these vascular and tracheal preparations, serotonin induced contractions via S 2 ‐serotonergic receptor sites. Ketanserin acted as a competitive antagonist. In contrast, ritanserin was un unsurmountable, apparently non‐competitive S 2 ‐serotonergic antagonist, except at the rabbit femoral artery where the serotonergic antagonism was of the competitive type. Its resistance to wash‐out suggests a long duration of action. Both compounds had little or no effect on serotonergic responses mediated through M‐ or D‐receptors in gastrointestinal tissues. In the femoral artery of the rabbit, ritanserin and ketanserin inhibited H 1 ‐histaminergic responses at concentrations 20 times and 4 times higher, respectively, than those required for S 2 ‐serotonergic antagonism. No other effects of ritanserin were observed unless at much higher concentrations. For instance, in the femoral artery of the rabbit, concentrations approximately 200 times higher (A 2 ‐value = 2.8 × 10 −8 M) were needed for alpha 1 ‐adrenergic antagonism than were required for S 2 ‐serotonergic antagonism (A 2 ‐ value = 1.3 × 10‐ 10 M), while this ratio was 9 for ketanserin for the same preparation. In the rat tail artery, these ratios, based on IC50‐values, were 666 and 39 for ritanserin and ketanserin respectively. In conclusion, as an S 2 ‐serotonergic antagonist, ritanserin is more potent and more specific than ketanserin. The mode of interaction with the S 2 ‐serotonergic receptor and the relation between time and antiserotonergic activity are different for the two compounds.
Type of Medium:
Online Resource
ISSN:
0272-4391
,
1098-2299
DOI:
10.1002/ddr.430080122
Language:
English
Publisher:
Wiley
Publication Date:
1986
detail.hit.zdb_id:
1500191-X
SSG:
15,3
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