The Animal Pharmacology of Buprenorphine, an Oripavine Analgesic Agent

Abstract

The general pharmacology of buprenorphine, a potent analgesic agent derived from oripavine, is described. 2 After acute administration of buprenorphine, the spontaneous locomotor activity of mice was increased; rats displayed stereotyped licking and biting movements; behavioural depresssion was marked in guinea-pigs but mild in rhesus monkeys. The behaviour of cats was unchanged. 3 In general, buprenorphine reduced heart rate but had no significant effect on arterial blood pressure in conscious rats and dogs. 4In anaesthetized, open-chest cats buprenorphine (0.10 and 1.0 mg/kg, i.v.) caused no major haemodynamic changes. 5 Buprenorphine (0.01-10 mg/kg, i.a.) and morphine (0.30-30 mg/kg, i.a.) increased arterial Pco2 values and reduced P02 values in conscious rats. With doses of buprenorphine greater than 0.10 mg/kg (a) the duration of respiratory depression became less, (b) ceiling effects occurred such that the maximum effects produced were less than those obtained with morphine. 6 Buprenorphine was a potent and long-lasting antagonist of citric acid-induced coughing in guineapigs.7 At a dose level 20 times greater than the ED50 for antinociception (tail pressure), morphine suppressed urine output to a greater extent than the corresponding dose of buprenorphine in rats. 8 Over the range 0.01-1.0 mg/kg (s.c.), buprenorphine slowed the passage of a charcoal meal along the gastrointestinal tract in rats. After doses in excess of I mg/kg, the meal travelled increasingly further such that the distances measured after 10 and 30 mg/kg did not differ significantly from control values. In contrast, the morphine dose-response relationship was linear.

Naltrexone–Buprenorphine Interactions: Effects on Cocaine Self-Administration

“…For example, behavioral studies have shown that the discriminative stimulus effects of buprenorphine could not be reversed by naltrexone given 25 minutes after buprenorphine, but could be prevented by naltrexone pretreatment in pigeons (France et al 1984) . Similarly, administration of naloxone after buprenorphine did not antagonize buprenorphine's effects in a discrimination paradigm (Shannon et al 1984) or on an analgesia measure in rats (Cowan et al 1977) . In clinical studies, naltrexone did not precipitate withdrawal signs or symptoms in bu prenorphine-maintained patients as it did in metha done-maintained patients (Kosten et al 1990).…”

“…However, the profIle of buprenorphine's recep tor binding in relation to its pharmacologic effects is not well understood and the kinetic and binding profIle of buprenorphine in the presence of naltrexone is un known. Buprenorphine's agonist and antagonist actions appear to have a bell-shaped dose-response curve on several measures (Cowan et al 1977;Lizasoain et al 1991;Pechnick et al 1985). Kinetic studies indicate that buprenorphine reaches peak plasma levels within 2 minutes after intravenous administration in man (Bul lingham et al 1980), within 2 to 5 minutes in baboon (Lloyd-Jones et al 1980), and rapidly reaches peak lev els in rodent and baboon brain within 10 to 15 minutes after administration (Holland et al 1989;Shiue et al 1991).…”

Analgesic effectiveness of the narcotic agonist‐antagonists.

“…In laboratory animals, buprenorphine produces some morphinelike effects, but it shows little capacity to produce physical dependence, and it is an antagonist of both morphine and etorphine (Cowan et al, 1977). In chronic spinal dogs, ceiling effects were noted to occur with graded single doses of buprenorphine and large doses of naloxone were required to precipitate abstinence in buprenorphine-dependent dogs.…”

Opioid agonist and antagonist behavioural effects of buprenorphine

“…Buprenorphine is a member of the oripavine series of narcotic structures and is a close analogue of the potent opioid agonist, etorphine and the antagonist diprenorphine (Cowan, Lewis & MacFarlane, 1977;Cowan, Doxey & Harry, 1977). Buprenorphine exhibits both opioid agonist and antagonist effects in laboratory animals.…”