1 Evidence is accumulating for multiple sigma (a) sites in the mammalian CNS. 2 We have addressed this problem and have examined a site -G-protein coupling in guinea-pig and rat brain membranes. 3 Ditolylorthoguanidine (DTG), (+ )-3-(3-hydroxyphenyl)-N-l-(propyl)piperidine (3PPP) and dextromethorphan displaced [3H]-DTG (3.4 nM) with low Hill slopes of 0.5, 0.6 and 0.6, respectively in guinea-pig brain membranes. 7 The heterogeneity of a sites appears to be less in rat than in guinea-pig brain membranes.

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