Naloxone suppresses buprenorphine stimulation of plasma prolactin.

The effects of parenterally-administered buprenorphine and simultaneous injection of naloxone was evaluated in six healthy adult males. Each subject was studied on six occasions, an average of 10 days apart, and received either two simultaneous intramuscular injections of saline, buprenorphine 0.3 mg and saline, or buprenorphine 0.3 mg and 0.6 mg, 0.45 mg, 0.3 mg, or 0.15 mg of naloxone. Simultaneous injection of buprenorphine 0.3 mg and saline resulted in an average increase in plasma prolactin above baseline levels of approximately 10 and 25 ng/ml, 30 and 55 minutes after injection. Buprenorphine-induced stimulation of plasma prolactin levels was statistically significantly greater than basal prolactin values (p less than 0.01). When 0.6 mg of naloxone was simultaneously injected with 0.3 mg buprenorphine, peak plasma prolactin levels were significantly lower (p less than 0.05) than prolactin values after administration of 0.3 mg buprenorphine and saline. Simultaneous injection of 0.45 mg naloxone and 0.3 mg buprenorphine also resulted in a significant attenuation (p less than 0.05) of buprenorphine-stimulated prolactin levels. Injection of 0.3 mg or 0.15 mg of naloxone did not inhibit prolactin stimulation produced by buprenorphine 0.3 mg. These findings demonstrate a dose-effect relationship between naloxone concentration and suppression of the increase in plasma prolactin levels produced by administration of buprenorphine 0.3 mg. As prolactin stimulation occurs shortly after opioid agonist administration and is temporally concordant with the rapid induction of pharmacologic reinforcement associated with opiate abuse, naloxone added to buprenorphine parenteral preparations may reduce the abuse potential of buprenorphine.