Figure 7.

Receptor selectivity of the antagonism by the cyclic tetrapeptides in the mouse 55°C warm-water tail-withdrawal test. Antinociceptive activity of morphine (10 mg/kg, i.p., left set of bars) was not reduced by a 3 h pretreatment of the mice with the cyclic tetrapeptides 2 (10 nmol, striped black bar), 3 (1 nmol, striped white bar), 4 (1 nmol, striped gray bar) or 5 (10 nmol, striped dark gray bar). However, the antinociceptive effect of U50,488 (10 mg/kg, i.p., center set of bars) was significantly antagonized by pretreatment of the mice with any of the cyclic tetrapeptides. (For this set of tests peptide 2 was administered at 3 nmol, i.c.v.). In contrast, the antinociceptive effect of SNC-80 (100 nmol, i.c.v., right set of bars) was significantly prevented only by pretreatment with peptides 3 and 5. Tail-withdrawal latencies were measured in the mouse 55°C warm-water tail-withdrawal test 40 minutes after injection of the known selective agonists. Data represents average % antinociception ± S.E.M. from 8-16 mice. * = significantly different from response of matching administered agonist alone, p<0.05, One-way ANOVA followed by Tukey’s HSD post hoc test.