Table 1.

Sigma-1 Receptor Affinity (K_D) and One-Site Linear Regression (R²) of N-Substituted Cocaine Derivatives. K_D and R² values of these compounds were calculated using GraphPad Prism software. (A) Competitive displacement curves against 10 nM (+)-[³H]pentazocine were generated, and data points were fit to a one-site nonlinear regression curve. R² values are reported to examine the “goodness of fit”. Haloperidol (5 μM) was used to determine nonspecific binding. (B) Structures of the N-substituted cocaine derivatives used in competitive displacement assays

A
Ligand	Sigma-1R KD (μM) (± SEM, n=3), R2	Sigma-2R KD (μM) (± SEM, n=3), R2	Ratio Sigma2/Sigma1
3	1300 (±401, 0.90)	a	Ndb
7	63 (±21, 0.98)	>40000	682.5
6	30 (±29.2, 0.86)	16.7 (±9.8, 0.91)	0.557
5	18.7 (±8.1, 0.95)	5350	286.1
8	10.97 (±3.2, 0.98)	N/a	Ndb

B

^aDoes not compete with [³H]-DTG

^bNd - not determined