Morphine, pharmacological action

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. ... 

Bioom AS, Dewey WL. (1978). A comparison of some pharmacological actions of morphine and deita9-tetrahydrocannabinoi in the mouse. Psychopharmacology (Berlin). 57(3) 243-48. 

Ramarao P, Bhargava HN. (1990). Antagonism of the acute pharmacological actions of morphine by Panax ginseng extract. Gen Pharmacol. 21(6) 877-80. 

Opium is the milky exudate obtained by incising the unripe seed capsule of the poppy plant Papaver somniferum and morphine is the most important alkaloid of opium. Morphine produces analgesia through action in the brain and spinal cord, that contain peptides possessing opioid like pharmacological action. These endogenous substances are known as endogenous opioid peptides (earlier known as endorphin now known as P-endorphin). 

Morphine and other opioids exert their pharmacological actions by acting on different receptors namely mu (p), kappa (k) and delta (5). 

Most often only one form shows correct physiological and pharmacological action. For example, only one enantiomer of morphine is active as an analgesic, only one enantiomer of glucose is metabolized in our body to give energy and only one enantiomeric form of adrenaline is a neurotransmitter. 

Pharmacological - actions at the same site. This is the typical agonist-antagonist competition for the same receptor. Atropine blocks the binding of acetylcholine. Naloxone blocks the binding of morphine. 

The pharmacological action of codeine is increased by induction as this increases demethylation to morphine. Induction by phenobarbital decreases the toxicity of organo-phosphates, but increases that of phosphorothionates. Studies with the drug warfarin have shown that induction by both phenobarbital and 3-methylcholanthrene will change the stereochemistry of the product, as can be seen in Table 5.24. Thus, hydroxylation in the 8-position in the R-isomer is increased 12 times compared with only 4 times with the S-isomer following 3-methylcholanthrene induction. 

Methadone, in general, exerts a pharmacological action similar to that of morphine. Its action on smooth muscle resembles that of meperidine. analgesic potency, but /-methodone is twice as effective. When used in comparable analgesic doses, methadone is as toxic as morphine and exerts the same effects on the pulse rate and respiration as does morphine. Methadone exerts no sedative effect and, hence, is of no value as a preanesthetic agent. 

Tramadol, however, is thousands of times less potent than morphine as an analgesic agent [18]. It is marketed in the racemic form, and each enantiomer has distinct pharmacological actions. The (+)-isomer is a weak MOP agonist, while the (-)-isomer inhibits neurotransmitter reuptake (norepinephrine and serotonin). The O-demethylated metabolite has improved opioid receptor affinity but is still much less potent (35-fold) than morphine. The ability for this metabolite to ameliorate the analgesic effects of tramadol has not been well studied and remains questionable. The drug has been used for decades in Europe, but was only recently introduced in the United States. It has a greater safety profile than morphine, and produces no respiratory depression or constipation. It is also claimed to be nonaddictive, but remains unscheduled. 

Laborit, H. Correlations between Protein and Serotonin Synthesis during Various Activities of the Central Nervous System (slow and desynchronized sleep, learning and memory, sexual activity, morphine tolerance, aggressiveness, and pharmacological action of sodium gamma-hydroxybutyrate). Research Communications in Chemical Pathology and Pharmacology 3 (1) (1972) 58-81. 

The morphine molecule possesses five asymmetric centers at carbons 5(R), 6(S), 9(R), 13(5), and 14(1 ), and it is this geometry that affords the familiar opioid pharmacological actions. The C-9 to C-13 ethanamino bridge restricts the number of possible optical isomers to 16 (i.e., eight racemic pairs). 

Morphine (1) and related compounds exert their major pharmacological actions on the central nervous system (CNS) and gastrointestinal tract (GIT). Their most important clinical property is the ability to induce analgesia, that is, to suppress pain, which they do without the patient necessarily losing consciousness. In addition, they induce drowsiness depress respiration, which may be life-threatening alter mood, often causing euphoria and physical... 

Goto(121 125) has prepared (+)-morphine and related structures from (—)-sinomenine. More recently, (+)-opioids have been required, not for their gross pharmacological actions, although these have been examined/126 but as research tools for probing opioid receptors/67 (+)-Codeine and (+)-morphine were synthesized 128 from (+)-dihydrocodeinone (60) derived in one step from sinomenine/124 Conversion of 60 to the ethyl carbamate (61) facilitated the... 

All of these series have pharmacological actions that parallel those of morphine, including dependence liability. They produce complete suppression of the abstinence syndrome in morphine-dependent monkeys, and their effects may be reversed by naltrexone. 

Papaverine Hydrochloride, USP. Papaverine hydrochloride. 6.7-dimelhoxy-l-veratryliso< uinoline hydrochloride. was isolated by Merck in 1848 from opium, in which it occurs to the extent of about Although its natural origin is closely related to morphine, the pharmacological actions of papaverine hydrochloride are unlike those of morphine. Its main effect is as a spasmolytic on smooth muscle, acting as a direct, nonspecific relaxant on vascular, cardiac, and other smooth muscle. Because of its broad antispas-modic action on ACh muscarinic receptors, it is often called a nonspecific antagonist. Papaverine hydrochloride has been used in the treatment of peripheral vascular disorders, but its u.se is limited by lack of potency. 

Tile general pharmacological action of codeine is similar 10 that of morphine, but as indicated above, it does not possess the same analgesic potency. Studies indicate that a dose uf. fO to 120 mg of ctxleinc is considerably less efficient uninterally than 10 mg of morphine, and the usual side effects of morphine—respiratory depression, constipation, nausea, and such—occur. Codeine is less effective orally lhan pareiitemlly, and Houde and Wallenstein stated that a do.se of. 52 mg of codeine is about as effective as 650 mg nf aspirin in relieving terminal cancer pain. Combinations... 

The major pharmacological actions of methadone, mediated by fi- and 6-receptor interactions, are similar to those of other opioids and include analgesia, sedation, respiratory depression, miosis, antitussive effects, and constipation. Methadone is administered as a racemic mixture (R,S- [ ] -methadone), but the analgesic activity is due almost entirely to the R(-)-isomer. When administered intramuscularly, methadone and morphine have equivalent analgesic potency. In contrast to morphine, methadone retains about 50% of its intramuscular analgesic potency when taken orally. ... 

Simonin F, Valverde O, Smadja C, Slowe S, Kitchen I, Dierich A, Le Mein M, Roques BP, Maldonado R, Kieffer BL (1998) Disruption of the kappa-opioid receptor gene in mice enhances sensitivity to chemical visceral pain, impairs pharmacological actions of the selective kappa-agonist U-50,488H and attenuates morphine withdrawal. EMBO J 17 886-897... 

Answer D. The pharmacologic action common to both morphine and D-tubocurarine is the release of histamine from mast cells, causing vasodilation. Morphine increases, but D-tubocurarine (via ganglion blockade) decreases, bladder tone. When used in combination with inhalational anesthetics (e.g., halothane), D-tubocurarine has been implicated in malignant hyperthermia. Morphine relaxes the uterus, but D-tubocurarine has no effects on smooth muscle neurotransmission. 

A synthetic peptide with morphine-like pharmacologic action Goldstein, Avram Goldstein, Joshua S. Cox, B. M. 

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