Morphine action

Bhargava H. N. Enhancement of morphine actions in morphine-naive and morphine-tolerant mice by LY 235959, a competitive antagonist of the NMDA receptor, Gen. Pharmacol. 1997, 28, 61-64. 

With the coagulation theory of morphine action and drug addiction substantiated, there appears to be no reason why certain morphine addicts should not be cured efficiently and completely by the use of sodium thiocyanate. 

Codeine (Methylmorphine) A prodrug 0% of dose is converted to morphine. Actions are due to morphine. Also an antitussive (suppresses coughing). Minor pain relief. Similar to morphine, but less intense at doses which relieve moderate pain. At high doses, toxicity is as severe as with morphine. 

Grewe R. Synthetic drugs with morphine action. Angew Chem 1947 A59 194-199. 

The actions of the naturally occurring materials now known as alkaloids were probably utilized by the early Egyptians and/or Sumarians (1). However, the beginnings of recorded, reproducible isolation from plants of substances with certain composition first took place in the early nineteenth century. Then in close succession, narcotine [128-62-1] (1, now called noscopine, C22H23NOy) (2) and morphine (2, R = H) (3) (both from the opium poppy, Papaver somnijerum E.) were obtained. 

P-Endorphin. A peptide corresponding to the 31 C-terminal amino acids of P-LPH was first discovered in camel pituitary tissue (10). This substance is P-endorphin, which exerts a potent analgesic effect by binding to cell surface receptors in the central nervous system. The sequence of P-endorphin is well conserved across species for the first 25 N-terminal amino acids. Opiates derived from plant sources, eg, heroin, morphine, opium, etc, exert their actions by interacting with the P-endorphin receptor. On a molar basis, this peptide has approximately five times the potency of morphine. Both P-endorphin and ACTH ate cosecreted from the pituitary gland. Whereas the physiologic importance of P-endorphin release into the systemic circulation is not certain, this molecule clearly has been shown to be an important neurotransmitter within the central nervous system. Endorphin has been invaluable as a research tool, but has not been clinically useful due to the avadabihty of plant-derived opiates. 

Morphine has certain undesirable side effects. Among these are respiratory depression, nausea, and vomiting, depression of the cough reflex, cardiovascular depression and hypotension, smooth muscle contraction (constipation), and histamine release (93). Morphine s onset of action, duration, and low therapeutic indices have prompted a search for a more effective opiate iv anesthetic. Extreme simplification of the complex morphine molecule has resulted in anilido —piperidines, the fentanyl class of extremely potent opiate iv anesthetics (118,119). 

A characteristic feature of the action of the opium alkaloids is their simultaneous depressing and exciting action on the central nervous system. In this respect there is no clear line of demarcation between the morphine group—morphine, codeine and thebaine—and the papaverine-narcotine group, and as the series is ascended in the order, morphine, papaverine, codeine, narcotine, thebaine, narcotic action diminishes and power of rellex stimulation increases until in thebaine a strychnine-like effect is exhibited. 

Morphine. This alkaloid exerts both a depressing and a stimulating action on the central nervous system, the depression affecting the brain especially the sensation of pain and the respiration the cerebral motoi functions are less affected. The stimulant action in the cord is best seen in the cold-blooded animals, when it may develop into tonic convulsions. In higher animals, but rarely in man, there may be some indication of this stimulant action. In cats it may also involve the motor areas, and they... 

These early observations on the correlation of structure and pharmacological action in the morphine group have been greatly extended as a result of chemical, pharmacological and clinical work done under the auspices of the American National Committee on Drug Addiction. In addition to numerous papers, contributed by experts serving this Committee, to chemical and pharmacological journals, two important reports have been published —... 

These general results have entailed much detailed chemical and pharmacological work on the influence of structural changes on particular items in the pharmacological action of morphine, e.g., its effect on respiration. ... 

Codeine (morphine methyl ether) resembles morphine in its general effect, but is less toxic and its depressant action less marked and less prolonged, whilst its stimulating action involves not only the spinal cord, but also the lower parts of the brain. In small doses in man it induces sleep, which is not so deep as that caused by morphine, and in large doses it causes restlessness and increased reflex excitability rather than sleep. The respiration is slowed less than by morphine (cf. table, p. 261). Cases of addiction for codeine can occur but according to Wolff they are rare. The best known ethers of morphine are ethylmorphine and benzyl-morphine [cf., table, p. 261), both used to replace morphine or codeine for special purposes. 

According to Eddy, as quoted by Small, the analgesic action of neopine, n omorphine, 6-acetylneomorphine or 3 6-diacetylneomorphine (p. 218) is definitely less than that of morphine and its corresponding analogues. The first two are about half as toxic as codeine and morphine respectively, and the second pair are more toxic than their morphine analogues. None of the four shows the Straub reaction and the convulsant action is less marked. 

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