Preservatives in the vehicle of naloxone: pharmacological effects

The pharmacological activity of the preservatives methyl and propyl hydroxybenzoate, until recently components of the vehicle of naloxone (Narcan), was investigated in vitro. This vehicle produced reversible, concentration-dependent relaxation of guinea pig trachea, not mediated via adrenergic or cholinergic receptors, prostanoid activity or phosphodiesterase inhibition. Sensitivity of the tissue to calcium-induced contraction was decreased. In single isolated rat hepatocytes, surface receptor stimulation elicits repetitive transient rises in intracellular free calcium measured with the photoprotein aequorin. The vehicle reversibly inhibited these transients. These observations suggest that the effect of hydroxybenzoates may be mediated via a perturbation of intracellular calcium-related processes.