8-Opioid activity

Similar to endogenous opioids, opiates like morphine and other synthetic opioids activate G-protein-coupled receptors which couple to G-proteins of the Gi/0 family. 

Since the discovery of the enkephalins in 1975 [11] a large number of endogenous opioid peptides have been detected in mammals, and at present three distinct families of opioid peptides are known (for a review, See Ref. 12). These are the enkephalins, the endorphins (a-, (J-, and y-), and the dynorphins and neoendorphins. The recently discovered endomor-phins [13] also may represent endogenous opioid peptides. Peptides with opioid activity have also been isolated from tryptic digests of milk casein... 

Table 3 In Vitro Opioid Activities and Receptor Affinities of Mixed p Agonist/6 Antagonists... 

Table 4 In Vitro Opioid Activities of Dipeptide 6-Opioid Agonists... 

Application of the concept of conformational restriction to opioid peptides has produced fruitful results, insofar as peptide analogues and mimetics with interesting opioid activity profiles and high stability against enzymatic... 

Opioid Activity During Pain , Proceedings of the National Academy of Sciences 104, no. 26 (2007) 11056-61... 

In the chemistry described in Scheme 6.151, Coats and a group of researchers from Johnson and Johnson utilized successive reductive aminations and Suzuki cross-coupling reactions to prepare a 192-member library of tropanylidene benz-amides [295], This series of tropanylidene opioid agonists proved to be extremely tolerant with regard to structural variation while maintaining excellent opioid activity. 

The answer is c. (Hardman, pp 574—575.) Phencyclidine is a hallucinogenic compound with no opioid activity Its mechanism of action is amphetamine-like. A withdrawal syndrome has not been described for this drug in human subjects. In overdose, the treatment of choice for the psychotic activity is the antipsychotic drug haloperidol. 

Both U-62066 (spiradoline) (10) and PD 117302 (12) are racemic mixtures of two enantiomers. The kappa opioid activity has been shown to reside in the (—) enantiomer, and in the case of U62066 the (-h) enantiomer is a weak mu receptor agonist [49, 50]. (See above for discussion on absolute stereochemistry.)... 

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... 

Pharmacology Diphenoxylate, a constipating meperidine congener, lacks analgesic activity. High doses cause opioid activity. 

The main objective of this experiment was to demonstrate that a peptide lead compound could be used in rational design of a non-peptide library. One of the natural opiates, met-enkephalin, is used as a hypothetical lead compound. The averaged frequency distribution based on four SA runs is obtained (data not shown). Based on this result, 03 had the highest frequency, and the frequencies of A4, Dll, D13, D14, D16, D2, D3, D5, and D9 are also above random expectation. Apparently, 03 appeared in all the reported active peptoids with opioid activity (cf. Table 1). Comparison of the structure of met-enkephalin (Fig. 5) with 03 indicated that 03 is similar to the side chain of tyrosine, which is the N-terminal residue of met-enkephalin. Among other building blocks found more frequently than random expectation, A4, D3, and D13 are present in the reported opioid peptoids (cf. Table 1). Thus, the SA sampling correctly identified four... 

Diphenoxylate is a synthetic meperidine analog with little or no analgesic activity. However in high doses it shows opioid activity such as euphoria and a morphine-like physical dependence after chronic administration. Its insolubility however, in aqueous solution prevents parenteral abuse. Nevertheless, diphenoxylate has in most countries been replaced by loperamide. 

One of the more benign ancillary activities of morphine lies in its activity in suppressing the cough reflex. Catalytic reduction of codeine (1-2) leads to the dihydro derivative (4-1). Oppenauer oxidation of the hydroxyl group leads to hydrocodone (4-2) [3], a compound used extensively in cough remedies it is of note, however, that this drug retains considerable opioid activity. 

It is a prodrug with no opioid activity itself. All its pharmacological activity derives from hydrolysis to monoacetylmorphine (MAM) and then to morphine in the plasma and tissues. Diamorphine also... 

Brandt, V. and Teschemacher, H. A material with opioid activity in bovine milk and milk products, Naunyn-Schmiedeberg s Arch. Pharmacol. 1979, 306, 301-304. 

Analgesic efficacy and clinical use Diphenoyxlate is a synthetic pethidine analog with a limited access to the brain and minimal analgesic activity. It has mainly peripheral opioid activity and oral administration induces inhibition of gastrointestinal motility and secretion. The compound is used for the treatment of acute and chronic diarrhea (Shee and Pounder, 1980 Lustman et al., 1987). 

Which is the more appropriate statement Opioids have endorphin activity, or endorphins have opioid activity Explain your answer. 

Fig. 10 17-nitrogen substituents of 4,5-epoxymorphinan derivatives and their opioid activities... 

The role of Gpy, released from pertussis toxin-sensitive G proteins, in coupling activated receptor to effectors further complicates specificity. Delta opioids activate G protein-coupled inwardly rectifying K+ channels [50] activation of such channels occurs by direct binding of Gp-y to various regions of the channel [51]. Delta agonist-mediated increase in the release of Ca2+ from intracellular stores in NG108-15 cells is mediated by Gp-y subunits [52], and Gp antibodies inhibited DPDPE stimulated PLC-p activation and, therefore, Ins(l,4,5)P3-dependent Ca2+ release and smooth muscle contraction in intestinal smooth muscle cells of the guinea pig [46]. However, the Ga... 

The Burroughs Wellcome compound collection was carefully studied in search of structures that might have opioid activity. Medicinal chemists considered the structures of the morphinoids as well as the enkephalins... 

TABLE 1 Delta and Mu Opioid Activity of Dimethylpiperazine Analogues3... 

After the disclosure of the structure and opioid activity of BW373U86, scientists outside of Burroughs Wellcome began exploring benzhydrylpiper-azine opioids, and made significant contributions to our understanding of the delta opioid receptor SAR. 

Although the mechanisms through which enhanced opioid activity may occur are not known, a complex interaction among p-opioid, 5-opioid, and chole-cystokinin (CCK) receptors has been proposed [153,162]. A basis for such interactions may lie in reports that CCK antagonizes morphine antinocicep-... 

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