μ Opiate receptors are selectively labelled by [3H]carfentanil in human and rat brain

Titeler, Milt; Lyon, Robert A.; Kuhar, Michael J.; Frost, James F.; Dannals, Robert F.; Leonhardt, Sigrun; Bullock, Amy E.; Rydelek, Laura T.; Price, Donald L.; Struble, Robert G.

doi:10.1016/0014-2999(89)90582-7

Cited by 72 publications

(47 citation statements)

References 13 publications

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“…Image data were then transformed on a voxel-by-voxel basis into two sets of parametric maps: (1) a tracer transport measure (K 1 ratio), and (2) a receptor-related measure [distribution volume ratio (DVR)], the latter using data obtained from 20 -70 min post-tracer administration for nonpainful control and pain studies. To avoid the need for arterial blood sampling, the tracer transport and binding measures were calculated using a reference region Logan plot analysis (Logan et al, 1996), using the occipital cortex (an area devoid of -opioid receptors) (Titeler et al 1989) as the reference region. With the tracer administration protocol used, the Logan plot becomes linear by 5-7 min after the start of radiotracer administration, with its slope being the DVR, a measure equal to the (f 2 Bmax/Kd) ϩ 1 for this receptor site and radiotracer.…”

Section: Methodsmentioning

confidence: 99%

Pronociceptive and Antinociceptive Effects of Estradiol through Endogenous Opioid Neurotransmission in Women

Smith¹,

Stohler²,

Nichols³

et al. 2006

J. Neurosci.

314

188

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Prominent interindividual and sex-dependent differences have been described in responses to sustained pain and other stressful stimuli. Variations in -opioid receptor-mediated endogenous opioid neurotransmission may underlie some of these processes. We examined both baseline -opioid receptor levels and the activation of this neurotransmitter system during sustained pain using positron emission tomography in a sample of young healthy men and women. Women were studied twice, during low and high estrogen states. The high-estrogen state was associated with regional increases in baseline -opioid receptor availability in vivo and a greater activation of endogenous opioid neurotransmission during the pain stressor. The latter did not differ from that obtained in males. During the low estrogen condition, however, significant reductions in endogenous opioid tone were observed at the level of thalamus, nucleus accumbens, and amygdala, which were associated with hyperalgesic responses. Estrogen-associated variations in the activity of -opioid neurotransmission correlated with individual ratings of the sensory and affective perceptions of the pain and the subsequent recall of that experience. These data demonstrate a significant role of estrogen in modulating endogenous opioid neurotransmission and associated psychophysical responses to a pain stressor in humans.

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Section: Methodsmentioning

confidence: 99%

Pronociceptive and Antinociceptive Effects of Estradiol through Endogenous Opioid Neurotransmission in Women

Smith¹,

Stohler²,

Nichols³

et al. 2006

J. Neurosci.

314

188

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“…In our previous study (McCaul et al, 2000b), levels of naltrexone and 6-b-naltrexol were very stable over consecutive days of administration of 50 mg naltrexone, with very low variability within individual subjects. Subjects underwent PET imaging using [ 11 C]CAR, a specific m-OR agonist (Frost et al, 1985;Titeler et al, 1989), and […”

Section: Race (N)mentioning

confidence: 99%

Differences in δ- and μ-Opioid Receptor Blockade Measured by Positron Emission Tomography in Naltrexone-Treated Recently Abstinent Alcohol-Dependent Subjects

Weerts

Kim

Wand

et al. 2007

Neuropsychopharmacol

139

147

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Blockade of brain m-opioid receptor (m-OR) and d-opioid receptor (d-OR) was investigated in recently abstinent alcohol-dependent subjects (N ¼ 21) maintained on naltrexone. Subjects completed a 19-day inpatient protocol, which included alcohol abstinence followed by naltrexone treatment (50 mg) on days 15-19. Blood samples were collected after the first administration of naltrexone to evaluate serum levels of naltrexone and 6-b-naltrexol. Regional brain m-OR binding potential (BP) and d-OR K i was measured using [ 11 C]carfentanil (CAR) positron emission tomography (PET) and [11 C]methyl naltrindole ([ 11 C]MeNTI) PET, respectively, before (day 5) and during naltrexone treatment (day 18). Naltrexone inhibition of [ 11 C]CAR BP was near maximal across all brain regions of interest with little variability across subjects (mean + SD% inhibition ¼ 94.9 + 4.9%). Naltrexone only partially inhibited the [ 11 C]MeNTI K i and there was more variability across subjects (mean + SD% inhibition ¼ 21.1 + 14.49%). Peak serum levels of naltrexone were positively correlated with % inhibition of d-OR K i in neocortex and basal ganglia. Peak serum levels of naltrexone were not correlated with % inhibition of m-OR BP. Peak levels of 6-b-naltrexol were not significantly correlated with % inhibition of m-OR BP or d-OR K i . Thus, the FDA recommended therapeutic dose of naltrexone was sufficient to produce near complete inhibition of the m-OR in recently abstinent alcohol dependent subjects. The lower percent inhibition of d-OR and greater variability in d-OR blockade by naltrexone across subjects may contribute to individual differences in treatment outcomes to naltrexone. Further investigations on the relationship between individual differences in d-OR blockade by naltrexone and clinical outcomes should be explored.

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“…The aqueous layer was extracted again with CHCWMeOH (31) (2 X 25 mL), the combined extracts were washed with saturated NaHCOs solution (15 mL) and water (15 mL) and dried (NazSOd, and the solvent was evaporated. The residue was chromatographed on silica gel usingEtOAc/hexane (32) as theeluanttogive thedeairedproduct 12 (45 mg 6@-Methyl-l+[ (2,2,2-trichloroethoxy)carbony1]-6,14dihy-dro-6,14-(epoxyimino)thebaine (16). A solution of 6.0 g of 58-methylthebaine (13) in200mLofEtOAcwasaddedtoamoled (0 "C) solution of 5.89 g of NdO4 in 150 mL of 0.5 M NaOAc solution at pH 6.0.…”

Section: (Pnitrocinnamoyl)amino]-7-anddihydrocodeinone (9)mentioning

confidence: 99%

14.beta.-[(p-Nitrocinnamoyl)amino]morphinones, 14.beta.-[(p-nitrocinnamoyl)amino]-7,8-dihydromorphinones, and their codeinone analogs: synthesis and receptor activity

Sebastian¹,

Bidlack²,

Jiang³

et al. 1993

J. Med. Chem.

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A series of 14 beta-[(nitrocinnamoyl)amino]codeinones and morphinones, some of which contain a 5 beta-methyl group, were prepared from 14 beta-aminocodeinones and 14 beta-[N-(cyclopropylmethyl)-amino]norcodeinones. The affinities of the target compounds for the mu, delta, and kappa opioid receptors were determined by radiolabeled binding experiments using bovine brain membranes. An analogous series of 7,8-dihydrocodeinones and morphinones was prepared and assayed in the same systems. The 3-methoxy derivatives 3 and 4 were more selective than the corresponding morphinones for the mu receptor. The 5 beta-methylcodeinones 25 and 27 had lower affinity at all receptors than the corresponding morphinones, but the 5 beta-methylmorphinones had affinities similar to the morphinones 5 and 6. A similar pattern was observed in the 7,8-dihydro series. Two compounds, 5 beta-methyl-14 beta-[(p-nitrocinnamoyl)amino]-7,8-dihydromorphinone, 20 (MET-CAMO), and N-(cyclopropylmethyl)-14 beta-[(p-nitrocinnamoyl)amino]-7,8-dihydronormorphinone, 22 (N-CPM-MET- CAMO), acted as nonequilibrium ligands in antinociception and membrane binding studies. In mice after icv administration, neither ligand showed any agonist activity but 8-24 h after administration both compounds acted as potent mu antagonists. A Scatchard plot of the effect of N-CPM-MET-CAMO on [3H]DAMGO ([3H]D-Ala2, (Me)-Phe4, Gly(ol)5] enkephalin) binding to bovine striatal membranes showed that there was a significant decrease in the Bmax value and a marginal effect on the Kd value suggesting that the number of binding sites was reduced. When taken together, these results support the view that 20 and 22 bind covalently to the mu receptor. On the other hand, when N-acetylcysteine and 22 were allowed to react in a buffered solution, 22 was recovered unchanged. Under these conditions no Michael reaction was observed.

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μ Opiate receptors are selectively labelled by [3H]carfentanil in human and rat brain

Cited by 72 publications

References 13 publications

Pronociceptive and Antinociceptive Effects of Estradiol through Endogenous Opioid Neurotransmission in Women

Pronociceptive and Antinociceptive Effects of Estradiol through Endogenous Opioid Neurotransmission in Women

Differences in δ- and μ-Opioid Receptor Blockade Measured by Positron Emission Tomography in Naltrexone-Treated Recently Abstinent Alcohol-Dependent Subjects

14.beta.-[(p-Nitrocinnamoyl)amino]morphinones, 14.beta.-[(p-nitrocinnamoyl)amino]-7,8-dihydromorphinones, and their codeinone analogs: synthesis and receptor activity

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