Table 1 Effect of OA agonists on the adenylate-cyclase activity in homogenates of American cockroach nerve cords in study seta

Compound       pKa   no. R Vmax (%) Ka (µM) Observed Calculatedb Deviationc       AAT       23 H (D) 34.21.1 215.24 (187.47-247.95) 3.67 3.34 0.33 24 H (L) 11.13.4 262.57 (193.61-344.80) 3.58 3.41 0.17 25 3-Br 13.40.9 154.00 (103.75-232.52) 3.81 3.35 0.46 26 3-Cl 19.00.6 157.63 (128.21-193.68) 3.8 3.99 -0.19 27 3-NO2 19.20.2 1407.55 (1083.37-1846.91) 2.85 3.58 -0.73 28 4-NO2 33.90 298.36 (280.53-317.65) 3.53 3.65 -0.12 29 4-CF3 31.81.5 99.82 (87.32-114.29) 4 3.66 0.34 30 4-MeO 8.80.5 3.51 (2.52-4.88) 5.45 5.85 -0.4 31 4-MeS 25.91.5 1033.02 (859.05-1247.86) 2.91 3.41 -0.5 32 4-Et 25.00.9 465.34 (387.24-556.93) 3.33 3.36 -0.03 33 2,3-Cl2 15.60.9 137.24 (82.00-212.16) 3.86 3.3 -0.56 34 2,4-Cl2 31.03.6 192.30 (165.79-223.06) 3.72 3.85 -0.13 35 2,4-Me2 11.60.9 217.75 (109.38-449.32) 3.66 3.34 0.32 36 2,5-F2 26.71.7 728.79 (585.31-921.35) 3.14 3.32 -0.18 37 2,6-(MeO)2 16.60.4 555.13 (334.87-917.15) 3.26 3.48 -0.22 38 3,5-Cl2 30.00.5 121.37 (98.43-149.89) 3.92 3.34 0.58 39 IND 13.80.8 581.64 (358.11-1025.27) 3.24 3.91 -0.67 40 THI 18.51.5 1328.80 (849.64-2218.85) 2.88 3.45 -0.57 41 Tyramine 22.45.6 24.88 (19.65-31.28) 4.6 4.79 -0.19       AIT       42 2-Br,4-Me 25.02.5 148.39 (136.27-161.37) 3.83 2.98 0.85 43 2-Me,4-Cl 36.73.8 3.09 (2.06-4.82) 5.51 5.62 -0.11 44 MCT6 16.00.8 205.01 (144.37-280.93) 3.69 3.14 0.55 45 DET5 13.31.2 151.32 (119.24-191.64) 3.82 3.5 0.32 46 DET6 39.83.6 158.92 (130.35-193.83) 3.8 3.17 0.63       SBAT       47 H 20.91.0 29.51 (17.86-56.69) 4.53 3.6 0.93 48 2-Cl 24.31.5 192.02 (105.91-315.60) 3.72 3.84 -0.12 49 2-F 29.10.6 162.88 (122.07-230.02) 3.79 3.55 0.24 50 3-CF3 26.13.3 69.55 (44.89-102.85) 4.16 4.58 -0.42 51 4-MeO 28.50.6 4.65 (3.06-6.99) 5.33 5.37 -0.04 52 2,4-Cl2 34.30.9 27.55 (18.99-38.81) 4.56 4.52 0.04 53 2-F,4-Cl 29.21.9 22.63 (18.86-27.11) 4.65 3.99 0.66 54 2,5-Cl2 27.92.2 8.91 (5.15-14.35) 5.05 4.37 0.68 55 2,6-(MeO)2 8.10.6 59.09 (23.25-141.57) 4.23 3.34 0.89 56 3-Cl,4-F 12.30.7 10.74 (3.93-22.72) 4.97 4.24 0.73 57 3,4-F2 19.32.9 80.36 (59.83-111.14) 4.09 4.89 -0.8 58 L-APAT 37.30.7 609.25 (552.91-672.55) 3.22 3.4 -0.18 59 D-APAT 16.01.2 328.60 (252.17-4321.21) 3.48 3.42 0.06 60 BPAT 22.70.6 185.65 (27.84-861.26) 3.73 4.44 -0.71       AIO       61 4-I 19.12.8 23.13 (17.18-31.01) 4.64 5.38 -0.74 62 2-Me,4-Br 33.92.3 19.54 (16.00-24.38) 4.71 5.04 -0.33 63 2,4-(MeO)2 29.92.1 31.24 (16.26-56.13) 4.51 3.65 0.86 64 2,6-iPr2 13.91.4 152.20 (100.57-219.87) 3.82 4.1 -0.28 65 2,3,4,5-Cl4 27.02.0 29.68 (24.45-36.23) 4.53 3.89 0.64 66 DCAO 28.60.7 14.71 (11.47-18.77) 4.83 4.65 0.18       SPIT       67 2-Me,4-Cl 30.60.4 1.99 (1.61-2.47) 5.7 4.96 0.74 68 2,4-Me2 10.50.5 34.64 (18.50-59.33) 4.46 5.34 -0.88 69 2-Me,5-Cl 10.80.7 201.47 (165.13-251.48) 3.7 3.89 -0.19 70 2,6-iPr2 23.80.3 59.49 (46.85-75.42) 4.23 4.29 -0.06

aSee the text for experimental details. The adenylate-cyclase activity of P. americana was measured according to Nathanson's procedure and the cAMP levels were measured by a RIA. Basal (control) and OA (100 mM)-stimulated (Vmax) adenylate cyclase activities were 116.25.4 and 1,473.359.3 pmol cAMP/min/mg of protein, respectively. In parentheses, 95% confidence limits are shown. Ka and 95% confidence limit values were calculated with the Macintosh personal computer system using a sigmoidal curve-fitting program designed for log dose-probit activity analyses. bCalculated by Equation (1). cIn case predicted activity is overestimated, deviation is obtained by calculating predicted activity subtracted by experimental value and indicated by minus. In case predicted activity is underestimated, deviation is obtained by calculating experimental activity subtracted by predicted value.