Summary of the results from in vitro studies showing the relative selectivity of RJR-2429 compared with that of nicotine and epibatidine. The parameters measured and the putative receptor(s) subtypes involved are indicated. An approximation of the measure of selectivity was derived by taking the relative potency, efficacy orKi values determined for nicotine or epibatidine. Rb represents ion flux from thalamic synaptosomes, DA represents dopamine release from striatal synaptosomes, HM represents ion flux from muscle nAChR in TE671/RD cells, and RG represents ion flux from nAChR in PC12 cells. Subscripts represent potency (p) and efficacy (e).
| Ki | Rbp | Rbe | DAp | DAe | SR | HMp | HMe | RGp | RGe | |
|---|---|---|---|---|---|---|---|---|---|---|
| Epibatidine* | 0.05 | 1 | ND | 0.4 | ND | 2.5 | 200 | ND | 110 | ND |
| Nicotine | 4 ± 0.3 | 591 ± 120 | 87 ± 22 | 100 ± 28 | 113 ± 17 | 0.17 | 80000 | 100 | 30000 | 100 |
| RJR-2429 | 1.0 ± 0.3 | >100,000 | <10 | 2 ± 1 | 40 | >50,000 | 59 ± 17 | 110 ± 09 | 1100 ± 230 | 85 ± 20 |
Ki, Rbp, DAp, HMp and RGp are expressed in nM.
Rbe, DAe, HMe and RGe are expressed as percentage of maximal activation by TMA (300 μM) for Rbe and DAe and as percentage of maximal activation with nicotine for HMe and RGe.
SR is the ratio of potencies for ion flux and dopamine release from thalamic and striatal synaptosomes, respectively.
* Data from Sullivan et al., 1994. ND: Not determined.