Raffa R B, Mathiasen J R, Goode T L, Vaught J L
Department of Biological Research, Janssen Research Foundation, Spring House, PA 19477-0776.
Life Sci. 1987 Oct 12;41(15):1831-6. doi: 10.1016/0024-3205(87)90702-8.
Intrathecal (IT) administration of pilocarpine to mice produces a vigorous and dose-related reciprocal hindlimb scratching (RHS) response (ED50 = 0.6 microgram) that is potently blocked by simultaneous IT administration of atropine (ID50 = 0.002 microgram). We now report that RHS is (1) also elicited by the more selective M1 agonist McN-A-343-11 (ED50 = 11.6 micrograms), (2) blocked by the selective M1 antagonist pirenzepine (ID50 = 0.001 microgram), and (3) is not blocked by the selective M2 antagonist AF-DX 116 BS at a dose up to 100 times the ID50 dose of pirenzepine. These results extend our earlier findings and suggest that the RHS elicited in mice by IT injection of muscarinic agonists is mediated through pirenzepine-sensitive (presumably M1) receptors and that RHS may be a convenient in vivo centrally mediated M1 endpoint.
向小鼠鞘内注射毛果芸香碱会产生强烈且与剂量相关的后肢交互搔抓(RHS)反应(半数有效量[ED50]=0.6微克),而同时鞘内注射阿托品能有效阻断该反应(半数抑制量[ID50]=0.002微克)。我们现在报告,RHS反应:(1)也可由选择性更强的M1激动剂McN-A-343-11引发(ED50=11.6微克);(2)可被选择性M1拮抗剂哌仑西平阻断(ID50=0.001微克);(3)在剂量高达哌仑西平ID50剂量100倍时,不会被选择性M2拮抗剂AF-DX 116 BS阻断。这些结果扩展了我们早期的发现,并表明鞘内注射毒蕈碱激动剂在小鼠中引发的RHS反应是通过对哌仑西平敏感(可能是M1)的受体介导的,并且RHS可能是一种方便的体内中枢介导的M1终点指标。