An analog of ACTH/MSH (4–9), ORG-2766, reduces cerebral uptake of morphine
7
Citation
40
Reference
10
Related Paper
Keywords:
Opiate
Basal (medicine)
This research sought to collate the effects of graded parenteral doses of codeine and morphine in 20 human male postaddicts. A six-point, double-blind, cross-over bioassay was used to contrast these drugs. Single intramuscular doses of codeine phosphate (90, 180 and 360 mg/70 kg) and morphine sulfate (7.5, 15 and 30 mg/70 kg) were compared in their production of miosis, drug identifications, opiate signs, opiate symptoms, liking (observers) and liking (subjects). Using these parameters, valid potency estimates were obtained which indicate that morphine is 7 to 14 times more potent than codeine. No significant decrement of effect in the doseresponse curve is demonstrated for either drug over these dose ranges for any of the parameters studied. Within these dose ranges, codeine and morphine produce notably similar patterns of identification, opiate signs and opiate symptoms. Codeine and morphine have a similar time action course for all variables except miosis, where codeine shows a more rapid onset and shorter duration of effect. Relative potencies calculated on the basis of total or peak data do not seriously differ in this investigation.
Opiate
Miosis
Morphine sulfate
Cite
Citations (17)
Intraventricular administration of the enkephalin analog, [D-Ala 2 ]-Metenkephalin, induces profound and long-lasting analgesia, as well as other opiate-like behavioral effects in the rat. This analgesia was highly dose dependent, of much greater magnitude, and about 30 times longer lasting than that produced by the naturally occurring peptide, methionine-enkephalin. The behavioral effects of the [D-Ala 2 ] analog could be completely reversed by the opiate antagonist, naloxone, suggesting that these effects were mediated by opiate receptors. Systemic administration of naloxone alone resulted in a significant increase in pain sensitivity. These findings support the view that endogenous opiate systems may play an important role in modulating pain sensitivity.
Opiate
Opiate receptors
Cite
Citations (159)
Opiate
Cite
Citations (20)
Evidence indicates that the neonate is capable, if not perceiving nociception, then at least reacting to nociceptive stimuli. These responses can be inhibited by opiates such as morphine. The analgesic potency of morphine in rat pups increases with maturation, due to (a) the proliferation of opiate receptors and (b), the maturation of supraspinal descending inhibition which becomes functional at 3 weeks post-natally. Tolerance to repeated injections of morphine in pups is less pronounced than in adults since it is masked by several processes, it has been demonstrated to occur within the first two weeks of life. Toxic effects of morphine in the neonate, as can be demonstrated both in behavior and EEG, differ from those in adults. Thus, convulsions induced by morphine which have been reported to occur in adults, were absent in pups. Excitatory effects of morphine in behavior develop in 3 different stages. During the first week morphine caused behavioral activation which is not mediated by specific opiate receptors. In the second week morphine produces EEG spikes in a dose-dependent fashion, but at this age these spikes were not reversible by opiate antagonists. Opiate specific EEG spikes and other opiate specific excitatory effects start to predominate during the third week of life.
Opiate
Convulsants
Opiate receptors
Cite
Citations (6)
A mixture of morphine-63H and morphine-N-14CH3 was administered to an opiate dependent and to a normal male subject. In both subjects the urinary excretion of radioactivity was rapid and exceeded 85% of the dose over 72 hours. The extent and time pattern of N-demethylation differed in the two subjects with N-demethylation of morphine being slower and less in the opiate addict. The use of the double isotope technique in detecting small changes in morphine metabolism is discussed.
Opiate
Demethylation
Nalorphine
Cite
Citations (3)
Opiate
Cite
Citations (5)
Opiate
Cite
Citations (10)
A series of cyclic, conformationally restricted analogs of somatostatin have been prepared and tested for their ability to inhibit the binding of [3H]naloxone and [D-Ala2, D-Leu5] [3H]enkephalin to rat brain membranes. The most potent analog, D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH2 where Pen is penicillamine in [D-Phe5, Cys6, Tyr7, D-Trp8, Pen11]somatostatin-(5-12)-octapeptide amide, exhibited high affinity for mu-opiate receptors (IC50 value of [3H]naloxone = 3.5 nM), being 7800 times more potent than somatostatin. The cyclic octapeptide also displayed high mu-opiate receptor selectivity with an IC50 [( D-Ala2,D-Leu5]enkephalin)/IC50 (naloxone) ratio of 271. The high affinity and selectivity of the somatostatin analog for mu-opiate receptors may be of use in examining the physiological role(s) of the mu-opiate receptor.
Opiate
IC50
Amide
Cite
Citations (108)
Photolabile derivatives of D-Ala2-Leu5-enkephalin were prepared by synthetic procedures in which a 2-nitro-4-azidophenyl group is linked to the terminal carboxyl group of the enkephalin by means of an ethylenediamine or ethylenediamine beta-alanine spacer. These peptides bind to opiate receptors with nanomolar affinities and inhibit electrically stimulated contractions of the mouse vas deferens and adenylate cyclase activity of NG108-15 neuroblastoma x glioma hybrid cell membranes. Both inhibitions are reversed by the opiate antagonist naloxone. Photolysis of the ligands bound to rat brain membranes results in the loss of approximately 50% of the receptor sites. This decrease in receptor number is blocked by naloxone and requires light. A photolabile [3H]enkephalin derivative labels an equivalent number of sites under similar irradiation conditions.
Ethylene diamine
Endorphins
Opiate
Vas deferens
Cite
Citations (21)
1. In rats injected repeatedly with a mixture of morphine and N-allylnormorphine in which the dose of the latter is too small to inhibit the analgesic effect of the morphine completely, the analgesic effect of the mixture declines more rapidly than it does to morphine alone. 2. It is demonstrated that this result is not due to tolerance to morphine, but to the greater inhibiting effect of N-allylnormorphine on morphine in partially tolerant than in non-tolerant rats. 3. Rats injected chronically with a morphine N-allylnormorphine mixture are less tolerant to morphine than are those injected for an equal length of time with morphine alone. 4. Rats injected chronically with N-allylnormorphine alone are more responsive to morphine than are normal animals.
Drug tolerance
Cite
Citations (35)