Morphine, application

Tetrahydropalmatine has strong analgesic, sedative, and hypnotic effects 544, 553-563). They are produced by the (—) type hut not by the (+) type. In rabbits the analgesic effect was weaker than that of morphine, but the tolerance for this drug developed at a far slower rate practically without any side effects. In experiments on patients tetrahydropalmatine had a weaker analgesic effect but a stronger hypnotic effect than morphine. Application of doses of 10 mg/kg of tetrahydropalmatine to white mice led to disappearance of the conditioned reflexes whereas the unconditioned reflexes were maintained. For the influence of (+ )-tetrahydropalmatine and other alkaloids on gastric ulcers in experimental animals, see Soji et al. (564). Variously substituted tetrahydroberberine and tetrahydropseudoberberine derivatives act as tranquilizers (565-569). 

Figure 1.1 Photography of mice showing the Straub tail response to morphine applications inset stamp of 1963 ornamented with a Straub tail response mouse. From Klaus Starke, Die Geschichte des Pharmakologischen lustituts der Universitat Freiburg, Figure 3, page 12. Reprinted by permission of Springer Science and Business Media.

In the post-World War II years, synthesis attained a different level of sophistication partly as a result of the confluence of five stimuli (1) the formulation of detailed electronic mechanisms for the fundamental organic reactions, (2) the introduction of conformational analysis of organic structures and transition states based on stereochemical principles, (3) the development of spectroscopic and other physical methods for structural analysis, (4) the use of chromatographic methods of analysis and separation, and (5) the discovery and application of new selective chemical reagents. As a result, the period 1945 to 1960 encompassed the synthesis of such complex molecules as vitamin A (O. Isler, 1949), cortisone (R. Woodward, R. Robinson, 1951), strychnine (R. Woodward, 1954), cedrol (G. Stork, 1955), morphine (M. Gates, 1956), reserpine (R. Woodward, 1956), penicillin V (J. Sheehan, 1957), colchicine (A. Eschenmoser, 1959), and chlorophyll (R. Woodward, 1960) (page 5). ... 

A particular interest for clinical applications was a possibility for detection of dopamine by its oxidation on nickel [19], cobalt [65], and osmium [66] hexacyanofer-ates. Except for oxidation of dopamine, cobalt and osmium hexacyanoferrates were active in oxidation of epinephrine and norepinephrine. For clinical analysis it is also important to carry out the detection of morphine on cobalt [67] and ferric [68] hexacyanoferrates, as well as the detection of oxidizable amino acids (cystein, methionine) by manganous [69] and ruthenium [70] hexacyanoferrate-modified electrodes. In general, oxidation of thiols was first shown for Prussian blue [71] and nickel hexacyanoferrate [72], This approach has been used for the detection of thiols in rat striatum microdialysate [73], Alternatively, the detection of thiocholine with Prussian blue was employed for pesticide determination in acetylcholine-esterase test [74],... 

Yaksh, T. L., Yeung, J. C., and Rudy, T. A., Systematic examination in the rat of brain sites sensitive to the direct application of morphine Observation of differential effects within the periaqueductal gray, Brain Res., 114, 83, 1976. 

Procedure Prepare the chromatogrphic tank by lining the walls with sheets of filter paper pour the mobile-phase into the tank, saturating the filter paper in the process, to a depth of 5 to 10 mm, close the tank and allow it to stand at 20° to 25 °C for 1 hour for equilibration of the mobile-phase in the chromatank. Apply separately to the TLC plate 5 (il of each of two solutions (1) and (2) of apomorphine hydrochloride and (3) of morphine in the form of circular spots about 2 to 6 mm in diameter, and 15 to 20 mm from one end of the plate and not nearer than 10 mm to the sides the two spots must be at least 10 mm apart. Mark the sides of the plate 15 cm from the line of application. Allow the solvent to evaporate and place in the chromatank,... 

Part—VI has been solely devoted to Miscellaneous Assay Methods wherein radioimmunoassay (RIA) (Chapter 32) has been discussed extensively. Various arms of theoretical aspects viz., hapten determinants and purity importance of antigenic determinants and analysis of competitive antibody binding of isotopically labeled compounds. The applications of RIA in pharmaceutical analysis, such as morphine, hydromorphone and hydrocordone in human plasma clonazepam, flurazepam in human plasma chlordiazepoxide in plasma barbiturates, flunisolide in human plasma have been described elaborately. Lastly, the novel applications of RIA-techniques, combined RIA-technique-isotope dilution and stereospecificity have also been included to highlight the importance of RIA in the analytical armamentarium. 

When an analyte is fluorescent, direct fluorometric detection is possible by means of a spectrofluorometer operating at appropriate excitation and observation wavelengths. This is the case for aromatic hydrocarbons (e.g. in crude oils), proteins (e.g. in blood serum, in cow milk), some drugs (e.g. morphine), chlorophylls, etc. Numerous fields of applications have been reported analysis of air and water pollutants, oils, foods, drugs monitoring of industrial processes monitoring of species of clinical relevance criminology etc. 

Opioids. Activation of opioid receptors in the enteric nerve plexus results in inhibition of propulsive motor activity and enhancement of segmentation activity. This antidiarrheal effect was formerly induced by application of opium tincture (paregoric) containing morphine. Because of the CNS effects (sedation, respiratory depression, physical dependence), derivatives with peripheral actions have been developed. Whereas diphenoxylate can still produce clear CNS effects, loperamide does not Lullmann, Color Atlas of Pharmacology... 

Dosages and routes of administration Morphine is available in different salt forms but the hydrochloride and sulfate (Vermeire and Remon, 1999) are used preferentially. The compound can be administered by the oral, parenteral or intraspinal route. Oral application is preferred for chronic pain treatment and various slow release forms have been developed to reduce the administration frequency to 2-3 times per day (Bourke et al., 2000). Parenteral morphine is used in intravenous or intramuscular doses of 10 mg, mostly for postoperative pain and self-administration devices are available for patient-controlled analgesia (PCA). Morphine is additionally used for intraspinal (epidural or intrathecal) administration. Morphine is absorbed reasonably well in the lower gastrointestinal tract and can be given as suppositories. 

Side-effects Morphine induces a variety of centrally- and peripherally-mediated side-effects. The most important of which is respiratory depression following parenteral administration, especially in the postoperative situation. Chronic oral application induces constipation and chronic treatment with oral morphine must be supplemented with laxatives. Other frequent side-effects are nausea, vomiting, dizziness and sedation. 

Marek, P., Ben-Eliyahu, S., Vaccarino, A. L., Liebeskind, J. C. Delayed application of MK-801 attenuates development of morphine tolerance in rats, Brain Res. 1991, 558, 163-165. 

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