Blockade of sensory nerve mediated contraction of the rabbit iris sphincter by a series of novel tachykinin antagonists.
Electrical stimulation of the isolated rabbit iris sphincter muscle in the presence of atropine gives rise to a contraction that can be blocked by tachykinin antagonists. The ability of a series of novel tachykinin antagonists to inhibit the contractile effect of SP on the guinea-pig taenia coli and to suppress the electrically evoked contraction of the atropinized rabbit iris sphincter was tested. Several of the novel antagonists were found to be more potent in terms of pA2 and pIC50 values than the two previously described analogs, [D-Pro2, D-Trp7,9]SP9(1-11) and [D-Arg1, D-Trp7,9, Leu11]SP-(1-11) (Spantide). Apart from D-Trp in positions 7 and 9 the characteristic features of the potent novel antagonists were D-Cl2Phe (or D-Cys(Bzl] in position 5, Asn in position 6 and Nle in position 11. In addition Pal in position 3 seemed to offer an enhanced potency.
D000818:Animals; D003106:Colon / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007498:Iris / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009479:Neuropeptides / Q000037:antagonists & inhibitors*; D009801:Oculomotor Muscles / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D013373:Substance P / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015320:Tachykinins
D009479:Neuropeptides; D015320:Tachykinins; D013373:Substance P