morphinans and Adenocarcinoma

Long-term treatment for more than 3 months with a central nervous system (CNS)-active drug, the opioid agonist bremazocine, at a dose of 1 mg/kg per day elicited an 80% inhibition of the volume of the subcutaneously transplanted rat prostate adenocarcinoma Dunning R3327H. Whereas, under this therapy, prostate tumour and prostatic weights were decreased, testes and pituitary weights remained normal. Bremazocine inhibited not only the growth of freshly transplanted tumours but also that of well-grown Dunning prostate carcinomas since, after 41 days of treatment, such tumours showed a volume inhibition of 52%. In these experiments bremazocine decreased LH and testosterone plasma levels significantly. Bremazocine, therefore, probably acts mainly through suprapituitary CNS-opiate receptor sites, which indirectly, rather than locally, mediate LH inhibition. Indeed, no specific receptors for bremazocine could be found in the Dunning tumour, which makes a local action of bremazocine in this tissue unlikely. the efficient tumour growth inhibition through the supra-pituitary action of bremazocine makes such opiate drugs, which lack respiratory and side effects due to improper use, of potential interest for treatment of prostatic tumours.

Topics: Adenocarcinoma; Animals; Benzomorphans; Central Nervous System; Luteinizing Hormone; Male; Morphinans; Organ Size; Prostate; Prostatic Neoplasms; Rats; Rats, Inbred Strains; Testosterone