Abstract
The effects of three tachykinin NK 1 receptor antagonists (L-668,169, (±)-RP 67580, and (±)-CP 96,345) were examined for their ability to antagonise responses evoked by substance P O-methyl ester (a selective NK 1 receptor agonist) in isolated neuronal tissue (rat superior cervical ganglia and guinea-pig locus coeruleus) and smooth muscle tissues (rat urinary bladder and guinea-pig ileum longitudinal muscle/myenteric plexus). (±)-RP 67580 was similarly effective in antagonising responses in both rat superior cervical ganglia and urinary bladder (estimated p K a value = 7.4 for both tissues); however, (±)-CP 96,345 was 50-fold less effective in antagonising responses in guinea-pig locus coeruleus than in ileum longitudinal muscle/myenteric plexus (estimated p K a values = 7.6 and 9.3 respectively). It is suggested that the differential effects of (±)-CP 96,345 may reflect the existence of a population of NK 1 receptors within guinea-pig locus coeruleus that are less sensitive to the effects of this NK 1 receptor antagonist.
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