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Memorias Do Instituto Oswaldo Cruz 1991We have recently studied several natural product constituents which have effects on the CNS. (1) Tetrahydropalmatine (THP) and its analogues were isolated from Corydalis... (Review)
Review
We have recently studied several natural product constituents which have effects on the CNS. (1) Tetrahydropalmatine (THP) and its analogues were isolated from Corydalis ambigua and various species of Stephania. (+)-THP and (-)-THP possess not only analgesic activity, but also exert sedative-tranquilizing and hypnotic actions. Results of receptor binding assay and their pre- and post-synaptic effects on dopaminergic system indicate that (-)-THP and (-)-stepholidine are dopamine receptor antagonists while (+)-THP is a selective dopamine depletor. (2) 3-Acetylaconitine (AAC) is an alkaloid isolated from Aconitum flavum. The relative potency of analgesic action of AAC was 5.1-35.6 and 1250-3912 times that of morphine and aspirin, respectively. The analgesic effect of AAC was not antagonized by naloxone, but was eliminated by reserpine. In monkeys, after AAC was injected for 92 days, no abstinence syndrome was seen after sudden AAC withdrawal or when challenged with nalorphine. (3) Huperzine A (Hup-A) is an alkaloid isolated from Huperzia serrata which was found to be a selective ChE inhibitor and could improve learning and retrieval processes. Preliminary clinical studies showed that Hup-A improve short- and long-term memory in patients of cerebral arteriosclerosis with memory impairment. (4) Ranamargarin is a new tetradecapeptide isolated from the skin of the Chinese frog Rana margaratae. This peptide may mainly act on NK-1 receptor.
Topics: Amino Acid Sequence; Animals; Central Nervous System Agents; Central Nervous System Depressants; Drug Evaluation, Preclinical; Drugs, Chinese Herbal; Humans; Memory Disorders; Molecular Sequence Data
PubMed: 1841995
DOI: 10.1590/s0074-02761991000600039 -
Anaesthesia Apr 1954
Topics: Morphine; Nalorphine
PubMed: 13148564
DOI: 10.1111/j.1365-2044.1954.tb01530.x -
Frontiers in Psychiatry 2021Opioids and stimulants are often used in combination for both recreational and non-recreational purposes. High-efficacy mu opioid agonists generally increase the...
Opioids and stimulants are often used in combination for both recreational and non-recreational purposes. High-efficacy mu opioid agonists generally increase the behavioral effects of stimulants, whereas opioid receptor antagonists generally attenuate the behavioral effects of stimulants; however, less is known regarding the interactions between stimulants and opioids possessing low to intermediate efficacy at the mu receptor. The purpose of this study was to examine the role of an opioid's relative efficacy at the mu receptor in altering the behavioral effects of dextro(-)amphetamine. To this end, opioids possessing a range of relative efficacy at the mu receptor were examined alone and in combination with cumulative doses of -amphetamine on a test of open-field, locomotor activity in male rats. Levorphanol, buprenorphine, butorphanol, nalbuphine, (-)-pentazocine, (-)-metazocine, (-)-cyclazocine, (-)-NANM, and nalorphine increased the locomotor effects of -amphetamine in either an additive or greater-than-additive manner according to an effect-additive model. Only the selective, high-efficacy kappa agonist, spiradoline, and the non-selective opioid receptor antagonist, naloxone, failed to increase the effects of -amphetamine under the conditions examined. These data indicate that opioids possessing a large range of relative efficacy at the mu receptor, including those possessing very low relative efficacy, significantly increase the locomotor effects of -amphetamine.
PubMed: 35069292
DOI: 10.3389/fpsyt.2021.790471 -
British Journal of Pharmacology Jun 19711. The predominant effect of morphine, diamorphine, pethidine or nalorphine on the blood pressure of the anaesthetized cat or rabbit is hypotension although,...
1. The predominant effect of morphine, diamorphine, pethidine or nalorphine on the blood pressure of the anaesthetized cat or rabbit is hypotension although, occasionally, a pressor action may predominate or intervene.2. Possible mechanisms of the depressor phases of action have been studied on cardiac and vascular preparations both in situ and in vitro.3. While in the whole animal, catecholamine release from the adrenal medulla and histamine liberation may be implicated in the responses, the vasodilator and vascular relaxant actions of morphine and, probably, pethidine, nalorphine and diamorphine on the isolated preparations are not mediated by the liberation of known peripheral transmitters or autacoids or by interaction with their specific receptors.
Topics: Acetylcholine; Adrenal Medulla; Animals; Aorta, Thoracic; Blood Pressure; Blood Vessels; Catecholamines; Cats; Depression, Chemical; Dilatation; Dopamine; Electrocardiography; Heart; Heroin; Histamine; Histamine Release; Isoproterenol; Meperidine; Methysergide; Morphine; Myocardium; Nalorphine; Nicotine; Norepinephrine; Perfusion; Portal Vein; Rabbits; Sensory Receptor Cells; Synaptic Transmission; Veins
PubMed: 4103858
DOI: 10.1111/j.1476-5381.1971.tb07098.x -
British Journal of Clinical Pharmacology 1979Two fundamentally different types of narcotic-antogonists have been found to be very effective analgesics with relatively low dependence-producing potentials. These...
Two fundamentally different types of narcotic-antogonists have been found to be very effective analgesics with relatively low dependence-producing potentials. These two drug classes can be distinguished as being either morphine-like or nalorphine-like on the basis of their subjective and objective effects after single doses and on chronic administration, and by the character of their abstinence syndromes on abrupt withdrawal or on precipitation by other antagonists. To explain differences in side effects associated with their analgesic actions, the existence of three types of receptors has been postulated: a μ receptor which is believed to be associated with euphoria and other typical morphine-like effects and a kappa (χ) and a sigma (σ) receptor which are believed to be associated with the sedative and psychotomimetic effects, respectively, of the nalorphine-like drugs. The antagonist-analgesics of the morphine-type have the characteristics of being agonists of low intrinsic activity but with high affinity for the μ receptor. Representative analgesics of this type are profadol, propiram and buprenorphine. The antagonist-analgesics of the nalorphine-type are drugs which are believed to have varying degrees of affinity and intrinsic activity at all three receptors, but characteristically seem to act merely as competitive antagonists with no intrinsic activity at the μ receptor. Representative analgesics of this type are pentazocine, nalbuphine and butorphanol. There are considerable differences among the individual drugs of each type in terms of their analgesic and narcotic-antagonistic potencies. However, clear differences in analgesic efficacy among any of the antagonist-analgesics remain to be proved. All give evidence of being capable of relieving pain in nondependent patients in situations in which doses of morphine (or its surrogates) usually used would be effective. The major advantages of the partial agonists of the morphine-type over the nalorphine-type drugs are that they have not been found to produce psychotomimetic reactions, and they seem to have fewer potentially deleterious effects in cardiac patients.
Topics: Morphine; Nalorphine; Narcotic Antagonists; Narcotics; Receptors, Opioid; Structure-Activity Relationship
PubMed: 223617
DOI: 10.1111/j.1365-2125.1979.tb04704.x -
British Journal of Pharmacology Jun 19971. Although it is well known that morphine induces significant immunosuppression, the potential immunosuppressive activity of morphine derived drugs commonly used in the...
1. Although it is well known that morphine induces significant immunosuppression, the potential immunosuppressive activity of morphine derived drugs commonly used in the treatment of pain (codeine, hydromorphone, oxycodone) has never been evaluated. 2. We evaluated in the mouse the effect of the natural opiates (morphine and codeine) and synthetic derivatives (hydromorphone, oxycodone, nalorphine, naloxone and naltrexone) on antinociceptive thresholds and immune parameters (splenocyte proliferation, Natural Killer (NK) cell activity and interleukin-2 (IL-2) production). 3. Morphine displayed a potent immunosuppressive effect that was not dose-related to the antinociceptive effect, codeine possessed a weak antinociceptive effect and limited immunosuppressive activity; nalorphine, a mu-antagonist and kappa-agonist, exerted a potent immunosuppressive effect, but had very weak antinociceptive activity. The pure kappa-antagonist nor-BNI antagonized the antinociceptive, but not the immunosuppressive effect of nalorphine. 4. Hydromorphone and oxycodone, potent antinociceptive drugs, were devoid of immunosuppressive effects. 5. The pure antagonists naloxone and naltrexone potentiated immune responses. 6. Our data indicate that the C6 carbonyl substitution, together with the presence of a C7-8 single bond potentiates the antinociceptive effect, but abolishes immunosuppression (hydromorphone and oxycodone). 7. The single substitution of an allyl on the piperidinic ring resulted in a molecule that antagonized the antinociceptive effect but maintained the immunosuppressive effect. 8. Molecules that carry modifications of C6, the C7-8 bond and C14, together with an allyl or caboxymethyl group on the piperidinic ring antagonized both the antinociceptive and the immunosuppressive effect of opiates and were themselves immunostimulants.
Topics: Animals; Cell Division; Codeine; Hydromorphone; Immune System; Immunosuppression Therapy; Interleukin-2; Male; Mice; Morphine; Nalorphine; Naloxone; Naltrexone; Narcotics; Oxycodone; Structure-Activity Relationship
PubMed: 9208156
DOI: 10.1038/sj.bjp.0701138 -
The International Journal of... Dec 2014Currently approved medications for opioid addiction have shown clinical efficacy, but undesired side effects, dependence induced by the medications themselves, and low...
BACKGROUND
Currently approved medications for opioid addiction have shown clinical efficacy, but undesired side effects, dependence induced by the medications themselves, and low treatment compliance necessitate the need for novel therapies.
METHODS
A novel morphine-keyhole limpet hemocyanin conjugate vaccine was synthesized with 6-glutarylmorphine as the hapten and a lengthened linker of 6 carbon atoms. The titer and specificity of the triggered antibody were assessed by enzyme-linked immunosorbent assay. The effects of the vaccine on the morphine-induced elevation of dopamine levels in the nucleus accumbens were determined by high-performance liquid chromatography. The effects of the vaccine on morphine-induced locomotor sensitization and heroin-primed reinstatement of heroin self-administration were also assessed.
RESULTS
After subcutaneous administration in rats, the vaccine triggered a high antibody titer, with comparable specificity for morphine, 6-acetylmorphine, and heroin, but no interaction with dissimilar therapeutic opioid compounds, including buprenorphine, naloxone, and nalorphine, was observed. The vaccine significantly prevented the elevation of dopamine levels in the nucleus accumbens induced by a single morphine challenge. Moreover, the vaccine prevented the expression of morphine-induced locomotor sensitization and heroin-primed reinstatement of heroin seeking, suggesting its potential for preventing relapse.
CONCLUSION
These results demonstrate that active immunization with the present vaccine induces a robust morphine/heroin-specific antibody response in rats and attenuates the behavioral effects of morphine and heroin.
Topics: Analgesics, Opioid; Animals; Antibodies; Behavior, Animal; Chromatography, High Pressure Liquid; Dopamine; Drug-Seeking Behavior; Heroin; Locomotion; Male; Morphine; Morphine Derivatives; Nucleus Accumbens; Rats; Rats, Sprague-Dawley; Reinforcement, Psychology; Self Administration; Treatment Outcome; Vaccines, Conjugate
PubMed: 25522425
DOI: 10.1093/ijnp/pyu093 -
British Medical Journal Jan 1967
Topics: Dextromoramide; Humans; Male; Middle Aged; Nalorphine; Substance Withdrawal Syndrome; Substance-Related Disorders
PubMed: 6066616
DOI: 10.1136/bmj.1.5532.88 -
European Journal of Pharmaceutical... Oct 2014The current study was designed to examine the sulfation of eight opioid drugs, morphine, hydromorphone, oxymorphone, butorphanol, nalbuphine, levorphanol, nalorphine,...
The current study was designed to examine the sulfation of eight opioid drugs, morphine, hydromorphone, oxymorphone, butorphanol, nalbuphine, levorphanol, nalorphine, and naltrexone, in HepG2 human hepatoma cells and human organ samples (lung, liver, kidney, and small intestine) and to identify the human SULT(s) responsible for their sulfation. Analysis of the spent media of HepG2 cells, metabolically labeled with [35S]sulfate in the presence of each of the eight opioid drugs, showed the generation and release of corresponding [35S]sulfated derivatives. Five of the eight opioid drugs, hydromorphone, oxymorphone, butorphanol, nalorphine, and naltrexone, appeared to be more strongly sulfated in HepG2 cells than were the other three, morphine, nalbuphine, and levorphanol. Differential sulfating activities toward the opioid drugs were detected in cytosol or S9 fractions of human lung, liver, small intestine, and kidney, with the highest activities being found for the liver sample. A systematic analysis using eleven known human SULTs and kinetic experiment revealed SULT1A1 as the major responsible SULTs for the sulfation of oxymorphone, nalbuphine, nalorphine, and naltrexone, SULT1A3 for the sulfation of morphine and hydromorphone, and SULT2A1 for the sulfation of butorphanol and levorphanol. Collectively, the results obtained imply that sulfation may play a significant role in the metabolism of the tested opioid drugs in vivo.
Topics: Analgesics, Opioid; Cytosol; Hep G2 Cells; Humans; Intestine, Small; Kidney; Liver; Lung; Narcotic Antagonists; Sulfates; Sulfotransferases; Sulfur Radioisotopes
PubMed: 24832963
DOI: 10.1016/j.ejps.2014.05.003