Pharmacokinetics of morphine in striatum and nucleus accumbens: relationship to pharmacological actions.
The pharmacokinetics of morphine was compared with its ability to increase striatal dopamine turnover (estimated by an increase in DOPAC concentration) and to produce the development of a muscular rigidity (estimated as a tonic activity in the electromyogram). After systemic administration of morphine (15 mg/kg IP), the concentration of morphine in blood plasma, striatum and substantia nigra showed a parallel time course with a maximum after 30 min; in the striatum, in addition, normorphine was found in a lower concentration, but with a similar time course. The elevation of striatal DOPAC, in contrast, commenced very rapidly and lasted for about four hours. The rigidity appeared later and disappeared earlier than the striatal DOPAC elevation. After unilateral intrastriatal injection of morphine (15 micrograms), a small amount of the drug penetrated very rapidly to distant sites, such as the contralateral striatum and nucleus accumbens, as well as to the ipsilateral nucleus accumbens. The results suggest that the relationship between pharmacokinetics and pharmacodynamics of morphine, both after systemic and after local injection into the brain, is more complex than could be expected from previous findings.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D004576:Electromyography; D007700:Kinetics; D008297:Male; D009020:Morphine / Q000378:metabolism* / Q000494:pharmacology; D009022:Morphine Derivatives / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009714:Nucleus Accumbens / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012686:Septal Nuclei / Q000378:metabolism*; D013997:Time Factors
D009022:Morphine Derivatives; D015102:3,4-Dihydroxyphenylacetic Acid; D009020:Morphine; C010616:normorphine