Pharmacodynamics and pharmacokinetics of intravenously administered morphine in spontaneously hypertensive and normotensive Wistar-Kyoto rats.

The analgesic and hyperthermic effects of i.v. administered morphine were determined in age-matched male spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. Two doses of morphine (5 and 10 mg/kg) were used. In the doses used, morphine produced analgesia in WKY rats as measured by the tail-flick test and expressed as area under the time-response curve. The intensity and duration of the analgesic area under the time-response curve was significantly greater in SHR rats in comparison to WKY rats. For example, whereas the effect of a 10-mg/kg dose lasted for 4 hr in WKY rats; in SHR rats the effect lasted for 10 hr. Similarly, the intensity and duration of morphine-induced hyperthermic response was greater in SHR rats in comparison to WKY rats. In order to determine if the differences in responses to morphine in SHR and WKY were related to its kinetics, the pharmacokinetic parameters of morphine in serum were determined. The area under the serum morphine concentration-time curve, serum levels of morphine extrapolated to zero time, T1/2, apparent volume of distribution at steady state, terminal elimination rate constant and total body clearance values for morphine in SHR and WKY rats did not differ. Previous studies from this laboratory indicate that the density of mu opiate receptors labeled with [3H]D-Ala2.MePhe4,Gly-ol5-enkephalin and [3H]naltrexone and of kappa-opiate receptors labeled with [3H]ethylketocyclazocine in the brain of SHR rats is higher than in WKY rats.(ABSTRACT TRUNCATED AT 250 WORDS)