The pure opiate antagonists, naloxone and naltrexone (0.1-10 mg/kg), dose-dependently suppressed water intake of 24 h water-deprived rats upon subcutaneous administration; their quaternary derivatives, methyl-naloxone and methyl-naltrexone, which are impermeable to the blood-brain barrier, failed to affect drinking. Upon intracerebroventricular administration, both quaternary analogs attenuated drinking at a dose of only 10 μg. These results demonstrate that the antidipsogenic effects of opiate antagonists are primarily mediated at sites within the central nervous system.
- quaternary narcotic antagonists
- site of action