Dalargin and [Cys-(O2NH2)]2 analogues of enkephalins and their selectivity for μ opioid receptors

Pencheva, Nevena; Ivancheva, Christina; Dimitrov, Emil; Bocheva, Adriana; Radomirov, R.

doi:10.1016/0306-3623(94)00244-h

Cited by 7 publications

(8 citation statements)

References 37 publications

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“…The present investigation provided more detailed and convincing data concerning the high potency and selectivity of dalargin for μ‐opioid receptors (Pencheva et al ., 1995, 1996). Comparison of the effects of dalargin, its analogues and endogenous enkephalins in models possessing different receptor populations in the presence and in the absence of peptidase inhibitors, allows us to characterize: (i) the tissues, in terms of their reliability for drug‐receptor classification; (ii) the opioid peptides in terms of their potency and selectivity; and (iii) the structure‐activity relationships, which are important for potency and selectivity of dalargin for μ‐opioid receptors.…”

Section: Discussionsupporting

confidence: 63%

“…The present investigation provided more detailed and convincing data concerning the high potency and selectivity of dalargin for m-opioid receptors (Pencheva et al, 1995(Pencheva et al, , 1996.…”

Section: Discussionsupporting

confidence: 55%

“…Some authors have reported that dalargin is selective for δ‐opioid receptors (Titov et al ., 1985), whilst others have reported mixed μ‐/δ‐activity (Korobov, 1988; Likhvantsev & Smirnova, 1991). Our earlier studies have shown a selectivity of dalargin for μ‐opioid receptors (Pencheva et al ., 1995, 1996). To further elucidate the structural features important for selective action of dalargin, a series of dalargin analogues, endogenous [Leu 5 ]‐ and [Met 5 ]‐enkephalin and μ‐selective agonist [D‐Ala 2 ,N‐Me‐L‐Phe 4 ,Gly‐ol 5 ]‐enkephalin (DAMGO) were tested for their effectiveness in depressing electrically‐evoked contractions in five bioassay tissues.…”

Section: Introductionmentioning

confidence: 99%

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Activity profiles of dalargin and its analogues in μ‐, δ‐ and κ‐opioid receptor selective bioassays

Pencheva¹,

Pospíšek²,

Hauzerová³

et al. 1999

British J Pharmacology

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1. To elucidate the structural features ensuring action of [D-Ala2, Leu5]-enkephalyl-Arg (dalargin), a series of dalargin analogues were tested for their effectiveness in depressing electrically-evoked contractions of the guinea-pig myenteric plexus-longitudinal muscle preparations (mu- and kappa-opioid receptors) and the vasa deferentia of the hamster (delta-opioid receptors), mouse (mu-, delta- and kappa-opioid receptors), rat (similar to mu-opioid receptors) and rabbit (kappa-opioid receptors). The naloxone KB values in the myenteric plexus were also obtained. 2. [L-Ala2]-dalargin was 19 times less potent than dalargin, and its pharmacological activity was peptidase-sensitive. The ratio of delta-activity to mu-activity for [L-Ala2]-dalargin was 6.78, and KB was 7.9 nM. This emphasizes the role that D-configuration of Ala2 plays in determining the active folding of dalargin molecule as well as in conferring resistance to peptidases. 3. [Met5]-dalargin was equipotent to dalargin in the myenteric plexus, but was more potent in the vasa deferentia of hamster and mouse (KB=5.5 nM). Leu5 and the interdependence of Leu5 and D-Ala2 are of importance for the selectivity of dalargin for mu-opioid receptors. 4. Dalarginamide was more potent and selective for mu-opioid receptors than dalargin, whilst dalarginethylamide, though equipotent to dalarginamide in the myenteric plexus, was more potent at delta-opioid receptors (KB=5.0 nM). [D-Phe4]-dalarginamide and N-Me-[D-Phe4]-dalarginamide were inactive indicating the contribution of L-configuration of Phe4 to the pharmacological potency of dalargin. 5. N-Me-[L-Phe4]-dalarginamide possessed the highest potency and selectivity for mu-opioid receptors (the ratio of delta-activity to mu-activity was 0.00053; KB=2.6 nM). The CONH2 terminus combined with the N-methylation of L-Phe4 increased the potency and selectivity of dalargin for mu-opioid receptors.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionsupporting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

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Activity profiles of dalargin and its analogues in μ‐, δ‐ and κ‐opioid receptor selective bioassays

Pencheva¹,

Pospíšek²,

Hauzerová³

et al. 1999

British J Pharmacology

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“…Opiate‐binding proteins from the synaptic membrane fraction were purified by affinity chromatography on solid matrix containing β‐endorphin22 or the novel opioid peptide dalargin (Tyr‐d‐Ala‐Gly‐Phe‐Leu‐Arg). Dalargin is the [Leu5]‐enkephalin analogue synthesized in the Scientific Cardiological Center (Moscow, Russia) and was shown to be the agonist of μ‐ and δ‐receptors 25,26…”

Section: Characterization Of Recombinant μ‐δ Receptormentioning

confidence: 99%

“…Dalargin is the [Leu5]-enkephalin analogue synthesized in the Scientific Cardiological Center (Moscow, Russia) and was shown to be the agonist of µand δreceptors. 25,26 The electrophoresis of total OBP r isolated from rat brain revealed three protein bands with molecular weights of 29, 45, 66 kDa, and those of M r 29, 65 for OBP h were purified from human synaptic membranes. 24 The electrophoretic point for both OBP r and OBP h was pI 5.4.…”

Section: Characterization Of Recombinant -␦ Receptormentioning

confidence: 99%

Recombinant μ‐δ Receptor as a Marker of Opiate Abuse

Dambinova

Izykenova

2002

Annals of the New York Academy of Sciences

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The brain is particularly vulnerable to drugs of abuse changing the neuroreceptor functions. Opiates interact and overstimulate heterogeneous opioid receptors leading to their desensitization, internalization, and activation of recombinant opioid receptor. The molecular properties of rat and human brain recombinant μ‐δ receptor were compared with those of purified μ‐ and δ‐receptors. cDNA coding the unique fragment of recombinant μ‐δ receptor was isolated and sequenced. We hypothesized that recombinant μ‐δ receptor may be a hallmark of opiate abuse. Peptide fragments of the μ‐ (MOR), δ‐ (DOR), and recombinant μ‐δ‐ (MDOR) receptors were used as antigens to assess the presence of autoantibodies in the blood of rats that self‐administered heroin and cocaine, as well as drug abusers. Significant steady elevation of MDOR autoantibodies were measured in sera of rats that self‐administered heroin compared to that for cocaine and vehicle animals. The appearance and increased level of MDOR autoantibodies in opiate abusers correlated with severity of the disorder and duration of drug exposure.

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[Cys(O2NH2)2]enkephalin analogues and dalargin: Selectivity for δ-opioid receptors

Pencheva¹,

Bocheva²,

Dimitrov³

et al. 1996

European Journal of Pharmacology

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Dalargin and [Cys-(O2NH2)]2 analogues of enkephalins and their selectivity for μ opioid receptors

Cited by 7 publications

References 37 publications

Activity profiles of dalargin and its analogues in μ‐, δ‐ and κ‐opioid receptor selective bioassays

Activity profiles of dalargin and its analogues in μ‐, δ‐ and κ‐opioid receptor selective bioassays

Recombinant μ‐δ Receptor as a Marker of Opiate Abuse

[Cys(O2NH2)2]enkephalin analogues and dalargin: Selectivity for δ-opioid receptors

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