Blood-brain barrier permeability and bioavailability of a highly potent and mu-selective opioid receptor antagonist, CTAP: comparison with morphine

D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) is a cyclic, penicillamine-containing octapeptide that is structurally similar to somatostatin and displays greater antagonist potency and selectivity for m-opioid receptors, compared with the classical m-selective antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2. The aim of this study was to determine whether CTAP can enter the central nervous system (CNS) by crossing either the blood-brain barrier or the blood-cerebrospinal fluid barrier (CSF) and to characterize the mechanism of CNS entry. CNS entry of [3H]CTAP was compared with that of the vascular space marker [14C]inulin and the m-agonist [3H]morphine. By using an in situ brain perfusion technique coupled to high-performance liquid chromatographic analysis, greater amounts of radioactivity were detected in the brain or CSF at most tim