Salvinorin A, the main psychoactive compound in Salvia divinorum, breaks down rapidly in rat plasma. At 37 degrees Celsius, its degradation rate constant was 3.8 x 10^(-1) per hour, much faster than at 4 degrees Celsius, where it was less than 6.0 x 10^(-3) per hour. The enzyme carboxylesterase primarily drives this breakdown, as inhibitors of that enzyme strongly suppressed degradation, while inhibitors of other esterases had little effect. The degradation products include salvinorin B (the deacetylated form) and lactone-ring-open forms of both salvinorin A and salvinorin B, with the ring-opening reactions involving a calcium-dependent lactonase.
The metabolism of methamphetamine (MA) and 4-bromo-2,5-dimethoxyphenethylamine (2C-B) was examined in freshly isolated rat hepatocytes and compared with in vivo results. For MA, the major metabolite was p-hydroxymethamphetamine, matching the urinary excretion profile in rats fed MA. For 2C-B, the major metabolites were 2-O-desmethyl-2C-B and a carboxylic acid derivative, a slight deviation from in vivo findings where 5-O-desmethyl-N-acetyl-2C-B predominated. Metabolites with a hydroxy group were largely conjugated, except for 2-O-desmethyl-2C-B. The primary hepatocyte culture system shows potential as a quick method for estimating the in vivo metabolic fate of abused drugs.