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Biomedical subjects

A E Takemori

Publications and source records attributed to A E Takemori.

At least 163 records · Page 9Linked to original sources
PubMed1980

The potentiation of spinal analgesia by leucine enkephalin.

In two strains of rats, intrathecal administration of morphine and met-enkephalin was found to produce a dose-dependent analgesic effect as measured by the tail-flick assay. Prior administration of leu-enkelphalin at a dose which had no analgesic effect was found to reduce significantly the analgesic ED50 of both morphine and met-enkephalin. Met-enkephalin pretreatment, at a similar sub-analgesic dose, was without effect. Thus, a differential interaction of the enkephalins with morphine is evident at spinal structures.

Anesthesia, Spinal↗
PubMed1980

Pharmacological studies with an alkylating narcotic agonist, chloroxymorphamine, and antagonist, chlornaltrexamine.

The 6-bis(2)chloroethyl)amino derivatives of oxymorphone and naltrexone, chloroxymorphamine (COA) and chlornaltrexamine (CNA), respectively, produce an irreversible inhibition of [3H]naltrexone binding to mouse brain homogenates. Intracerebroventricular (i.c.v.) injection of COA (4 nmol/mouse) elicits analgesia which lasts 4 times longer than analgesia produced by equimolar and equieffective dose of oxymorphone. The analgesia induced by COA can be reversed and blocked by naloxone. Injections of both COA and CNA i.c.v. antagonize morphine-induced analgesia for 3 days. Similarly, when [3H]naltrexone binding is measured in brains from mice pretreated i.c.v. with COA or CNA, there is a significant decrease in total specific binding for 3 days after pretreatment. These data suggest that CNA and COA alkylate the opioid receptors to produce antagonist and agonist-antagonist effects, respectively. The implications of these findings are discussed with respect to their effect on our perception of the opioid receptor-narcotic agonist interaction and the mechanisms of tolerance and dependence.

Analgesics↗
PubMed1979

Chloroxymorphamine, and opioid receptor site-directed alkylating agent having narcotic agonist activity.

Chloroxymorphamine, the 6beta-N,N-bis(2-chloroethyl) derivative of oxymorphone, is a potent nonequilibrium narcotic agonist in the longitudinal muscle preparation of guinea pig ileum. The corresponding naltrexone analog,chlornaltrexamine, is a potent nonequilibrium antagonist of morphine. These receptor sitedirected alkylating agents possess considerable potenial as pharmacologic and biochemical probes of apoid receptors.

Alkylating Agents↗
PubMed1979

The effect of dopaminergic modifiers on morphine-induced analgesia and respiratory depression.

The influences of the dopaminergic system on morphine-induced analgesia and respiratory depression were compared using modulators of dopaminergic activity. Blockade of dopaminergic receptors by haloperidol or pimozide produced a potentiation of morphine analgesia, while stimulation of dopaminergic activity by L-dopa methyl ester inhibited morphine analgesia. Morphine-induced depression of respiratory rate was potentiated by haloperidol and inhibited by pimozide or L-dopa methyl ester. These results suggest that the dopaminergic system plays a modulating role in morphine-induced analgesia, but not in morphine-induced respiratory depression.

Analgesics, Opioid↗
PubMed1979

Enhanced naloxone potency and the development of narcotic tolerance.

When various biogenic amine modifying drugs were administered to mice which were pretreated with morphine, none of the drugs except atropine and haloperidol altered the usual doubling of the naloxone efficacy which is observed in morphine-pretreated mice. Atropine appeared to decrease the potency of naloxone. Haloperidol, which did not alter naloxone potency in normal mice, further increased the naloxone potency in morphine-pretreated mice. When the biogenic amine modifiers were injected chronically to mice during the development of morphine tolerance, again none of the drugs, except haloperidol and atropine altered the development of tolerance. Haloperidol appeared to enhance and atropine to inhibit the degree of tolerance. These results indicate that it is the alteration in the narcotic-induced enhancement of naloxone potency and not the mere alteration of noloxone potency by various drugs, which can be used as an indicator of the alterations in the development of tolerance.

Animals↗
PubMed1979

Improved method for morphine extraction from biological samples.

Methadone morphine, or naloxone extraction from brain homogenates, plasma, and urine is described. An aqueous sample was loaded on a surgical gauze support, which was washed with extracting solvents. Aqueous samples remained on the support, and nonpolar drugs partitioned into the lipophilic extracting solvent. The procedure recovered 80-100% of nanogram levels of methadone, morphine, or naloxone from biological samples. In addition, an approximate 10-fold timesaving capacity was demonstrated compared to standard liquid-liquid extraction techniques.

Animals↗
PubMed1979

Synthesis and pharmacologic characterization of an alkylating analogue (chlornaltrexamine) of naltrexone with ultralong-lasting narcotic antagonist properties.

Chlornaltrexamine (CNA) produces ultralong-lasting (3--6 days) narcotic antagonism in mice and persistent stereospecific binding to rat-brain homogenate. Protection studies in mice suggest that CNA mediates its narcotic antagonist effects by interacting with the same receptors that are occupied by naloxone. A single icv dose of CNA also has been found to inhibit the development of physical dependence in mice for at least 3 days. These studies suggest that CNA exerts its sustained effects by selective covalent association with opioid receptors.

Alkylating Agents↗
PubMed1979

Differential effects of leucine and methionine enkephalin on morphine-induced analgesia, acute tolerance and dependence.

Intracerebroventricular (40-80 microgram) or i.p. (5-20 mg/kg) injection of leucine enkephalin 15 min before or after s.c. morphine administration resulted in a marked, dose-dependent enhancement of morphine analgesia as measured by the mouse tail-flick assay. Further, i.p. injection of leucine enkephalin (5 mg/kg) enhanced the analgesia produced by methadone and levorphanol in the tail-flick assay but not that by nalorphine in the abdominal constriction assay. Met- but not leu-enkephalin was an active analgesic in the abdominal constriction assay with the doses used. (D-Ala2, D-leu5)-enkephalin (1 mg/kg) treatment also markedly enhanced morphine analgesia. Similarly, administration of leucine enkephalin enhanced the development of acute tolerance and dependence produced by a single dose of morphine. Methionine enkephalin had no effect on any of the pharmacological responses produced by morphine, methadone or levorphanol. Morphine brain levels of mice after treatment with leucine or methionine enkephalin were found to be no different than those of saline-treated control animals. These results suggest that leucine enkephalin may be an important and potent physiological modulator of narcotic efficacy.

Analgesia↗
PubMed1978

Antagonism by naloxone of narcotic-induced respiratory depression and analgesia.

Receptor mechanisms for narcotic-induced respiratory depression and analgesia were compared by apparent pA2 values of morphine-naloxone, levorphanol-naloxone and pentazocine-naloxone. The similarity of apparent pA2 values of the three compunds for respiratory depression suggests that morphine, levorphanol and pentazocine may interact with similar receptors to produce this effect. Significant differences between apparent pA2 values of pentazocine-naloxone and morphine-naloxone or levor-phanol-naloxone for analgesia suggest, as previously shown, that narcotic and narcotic-antagonist analgesics appear to interact with receptors in different manners. Significant differences between apparent pA2 values for respiratory depression and analgesia suggest that these two effects of the narcotic drugs are mediated by different receptor interactions.

Analgesics, Opioid↗