Peripheral benzodiazepine binding sites: Effect of PK 11195, 1-(2-chlorophenyl)-n-methyl-n-(1-methylpropyl)-3-isoquinolinecarboxamide

Fur, G. Le; Perrier, M.L.; Vaucher, Nadine; Imbault, F.; Flamier, A.; Bénavidès, J.; Uzan, A.; Renault, C.; Dubroeucq, Marie-Christine; Guérémy, C.

doi:10.1016/0024-3205(83)90062-0

Cited by 309 publications

(61 citation statements)

References 7 publications

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“…A second, more ubiquitously expressed BZD binding site is found on the outer mitochondrial membranes of peripheral tissues and cells (6,(10)(11)(12). This latter site, the so-called peripheral-type BZD receptor (PBR), is characterized by its affinity for another BZD ligand, Ro5-4864, and the isoquinoline derivative PK11195, rather than for clonazepam (6,13,14). A number of PBR ligands have been shown to influence a variety of cell processes, including adrenal steroidogenesis (15)(16)(17)(18)(19)(20)(21)(22), mitochondrial respiration (23), and the growth and differentiation of murine cell lines (5,6,24,25).…”

mentioning

confidence: 99%

Tumor selective G ₂ /M cell cycle arrest and apoptosis of epithelial and hematological malignancies by BBL22, a benzazepine

Xia

Spector

Hardy

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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mentioning

confidence: 99%

Tumor selective G ₂ /M cell cycle arrest and apoptosis of epithelial and hematological malignancies by BBL22, a benzazepine

Xia

Spector

Hardy

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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“…(0.01 M) / MeOH MeCN / AcOH (70: 2 2 7: I by vol.). A single radioactive peak with the same retention time (12 min) as authentic viqualine (I) was observed. The specific activity of [O-merhyl-11C]viqualine (II), decay-corrected to EOB, (S,) was calculated from the radioactivity (Ay GBq) in the collected peak, measured in a calibrated high pressure ionisation chamber at t min from EOB, and from the mass of compound (M, p o l )…”

Section: Analysis Of Nca [U-methyz-11c]viqualine (11)mentioning

confidence: 91%

“…50 of 3 nM (12) and also the binding of another potent 5HT reuptake site ligand,[3H]indalpine, to rat brain sections with a Ki of 0.48 nM (13). This inhibition is highly selective for 5 HT (12).…”

mentioning

confidence: 99%

The radiosynthesis of nca [O‐methyl‐¹¹C]viqualine, through an N‐trityl‐protected intermediate, as a potential pet radioligand for 5HT re‐uptake sites

Pascali

Pike

Turton

1990

Labelled Comp Radiopharmac

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Summarv Viqualine, (4-[3-[3(R)-ethenyl-4(R)-pipcridinyl]propyl]-~methoxyquino~~e), has been labelled in the 0-methyl position with nocarrier-added (ma) carbon-1 1 (tllz = 20.4 min; p+ = 99.8%) to provide a potential radioligand for PET studies of 5HT re-uptake sites. Direct treatment of desmethyl-viqualine with nca [ 11Cliodomethane gave [O-methyl-1lC]viqualine as only a minor product. NMR data suggested that the dominant product is that from the [W]alkylation of the competing piperidino-nitrogen. Rotection of this nitrogen with the trityl group, followed by treatment with nca [ 11C]iodomethane in dimethyl sulphoxide with sodium hydroxide as base, and then rapid deprotection by mild acid hydrolysis gave nca [O-methyl-11C]viqualine as the main crude product (27% radiochemical yield, decay-corrected from [ 11Cfiodomethane). Radiochemically and chemically pure nca [O-methyl-llCIviqudine was obtained by work up on C18 Sep-pak followed by reverse phase HPLC. The radiosynthesis. including final formulation for i.v. administration, takes 56 min after producing the carbon-11 as [11C]carbon dioxide by the 14N(p,a)W reaction. This radiosynthesis illustrates the potential utility of the mtyl group for the protection of nitrogen in rapid carbon-1 1 radiochemistry. Key words:[11C]viqualine. 5HT re-uptake site, radioliogand, PET, N-trityl I "Positron emission tomography (PET) (1) is now widely explored as a technique for investigating pathophysiology in living man, especially for measuring neurotransmitter systems whose dysfunction may play a role in the progress of poorly understood neuropsychiamc disease (for reviews see references 2-4). Much in vitro and post mortem evidence now implicates a dysfunction in serotonergic neurotransmission in clinical depression (for an overview see reference 5). One hypothesis is that depression results from a deficiency in serotonin (5HT) and hence that the well known tricyclic antidepressants counter this deficiency by specifically inhibiting the presynaptic re-uptake of SHT. More recent hypotheses implicate abnormal levels of either presynaptic 5HT re-uptake sites or post-synaptic 5 m 2 receptors.Clearly, suitably radiolabelled markers of the serotonergic system might allow the aetiology of depression to be investigated by PET in living man. One approach is to develop a radioligand

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“…These drugs were chosen to represent the different classes of benzodiazepine ligands, peripheral-type and central-type (including agonist, antagonist, partial inverse agonist). We also used two flavones (ACA6 and MP37) which exhibit inhibitory effects on platelet aggregation (Beretz & Cazenave, 1988 In an attempt to compare these values with the previously published ones (Wang et al, 1980;Le Fur et al, 1983;Benavides et al, 1984) we calculated the corresponding K; from IC50 values (Table 1). We found a slightly lower affinity for both PK 11195, Ro 4864 and diazepam (K.: 39, 299, 551 nm, respectively) than those previously described (K;: 4, 22, 194nm, respectively Gardner (1988 (Figure 3).…”

Section: Aggregation Studiesmentioning

confidence: 99%

Benzodiazepine analogues inhibit arachidonate‐induced aggregation and thromboxane synthesis in human platelets

Fonlupt¹,

Croset

Lagarde

1990

British J Pharmacology

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Benzodiazepine analogues inhibit human platelet aggregation induced by arachidonate with an EC50 value of 0.68 μm for PK 11195, the most potent analogue used. There was a highly significant correlation between the inhibition of arachidonate‐induced aggregation and the affinity for the peripheral‐type of benzodiazepine binding sites. There was no significant correlation between the inhibition of the platelet activating factor (PAF)‐induced aggregation and the binding to the peripheral‐type of benzodiazepine binding sites. The inhibition of platelet aggregation seems to result from the inhibition of arachidonic acid cyclooxygenation, since the synthesis of thromboxane and 12‐hydroxy‐heptadecatrienoic acid, both cyclooxygenase products, was reduced. Our results suggest that peripheral‐type of benzodiazepine binding sites on human platelets could be linked to cyclo‐oxygenase.

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Peripheral benzodiazepine binding sites: Effect of PK 11195, 1-(2-chlorophenyl)-n-methyl-n-(1-methylpropyl)-3-isoquinolinecarboxamide

Cited by 309 publications

References 7 publications

Tumor selective G ₂ /M cell cycle arrest and apoptosis of epithelial and hematological malignancies by BBL22, a benzazepine

Tumor selective G ₂ /M cell cycle arrest and apoptosis of epithelial and hematological malignancies by BBL22, a benzazepine

The radiosynthesis of nca [O‐methyl‐¹¹C]viqualine, through an N‐trityl‐protected intermediate, as a potential pet radioligand for 5HT re‐uptake sites

Benzodiazepine analogues inhibit arachidonate‐induced aggregation and thromboxane synthesis in human platelets

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Peripheral benzodiazepine binding sites: Effect of PK 11195, 1-(2-chlorophenyl)-n-methyl-n-(1-methylpropyl)-3-isoquinolinecarboxamide

Cited by 309 publications

References 7 publications

Tumor selective G 2 /M cell cycle arrest and apoptosis of epithelial and hematological malignancies by BBL22, a benzazepine

Tumor selective G 2 /M cell cycle arrest and apoptosis of epithelial and hematological malignancies by BBL22, a benzazepine

The radiosynthesis of nca [O‐methyl‐11C]viqualine, through an N‐trityl‐protected intermediate, as a potential pet radioligand for 5HT re‐uptake sites

Benzodiazepine analogues inhibit arachidonate‐induced aggregation and thromboxane synthesis in human platelets

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Product

Resources

About

Tumor selective G ₂ /M cell cycle arrest and apoptosis of epithelial and hematological malignancies by BBL22, a benzazepine

Tumor selective G ₂ /M cell cycle arrest and apoptosis of epithelial and hematological malignancies by BBL22, a benzazepine

The radiosynthesis of nca [O‐methyl‐¹¹C]viqualine, through an N‐trityl‐protected intermediate, as a potential pet radioligand for 5HT re‐uptake sites