Conversion of chlorpromazine sulfoxide to chlorpromazine by use of metals in acid solution

Korczak-Fabierkiewicz, C.; Robinson, Dan; Lucas, George H. W.

doi:10.1016/s0021-9673(01)86108-2

Cited by 4 publications

(2 citation statements)

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“…Stock solutions of [ 3 H]CPZ in ethanol were unstable over time, with [ 3 H]CPZsulfoxide the major degradation product. When needed, oxidized [ 3 H]CPZ (375 μCi) in 0.11 mL methanol/0.01 N HCl was reduced by exposure to metallic zinc (15 mg) for 2 h at room temperature (26), and then [ 3 H]CPZ was purified by thin layer chromatography. For preparative photolabeling experiments leading to the identification of photolabeled amino acids, freshly synthesized [ 3 H]CPZ was used at a purity >95%.…”

Section: Methodsmentioning

confidence: 99%

[³H]Chlorpromazine Photolabeling of the Torpedo Nicotinic Acetylcholine Receptor Identifies Two State-Dependent Binding Sites in the Ion Channel

et al. 2009

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Chlorpromazine (CPZ), a potent nicotinic acetylcholine receptor (nAChR) noncompetitive antagonist, binds with higher affinity in the ion channel in the desensitized state than in the closed channel state and with low affinity to additional sites in nAChR-rich membranes. For nAChR equilibrated with agonist, we confirm previous reports that [3H]CPZ occupies a site near the cytoplasmic end of the M2 ion channel domain, photolabeling positions M2-2, M2-6 and/or M2-9 in each subunit. We find that [3H]CPZ also binds at the extracellular end of the channel, photolabeling amino acids at positions M2-16 (α,γ), M2-17 (α,β,δ), and M2-20 (α,β,δ). The photolabeling at the cytoplasmic end of the channel is fully inhibitable by phencyclidine or proadifen, whereas neither drug inhibits [3H]CPZ photolabeling at the extracellular end, establishing that positively charged drugs can bind simultaneously at the cytoplasmic and extracellular ends of the ion channel. [3H]CPZ photolabeling is not detected in the transmembrane domain outside the ion channel, but it photolabels αMet-386 & αSer-393 in the cytoplasmic αMA helix. In the nAChR equilibrated with α-bungarotoxin to stabilize the nAChR in a closed state, [3H]CPZ photolabels amino acids at M2-5 (α), M2-6 (α,β,δ) and M2-9 (β,δ), with no labeling at M2-2. These results provide novel information about the modes of drug binding within the nAChR ion channel and indicate that within the nAChR transmembrane domain, the binding of cationic aromatic amine antagonists can be restricted to the ion channel domain, in contrast to the uncharged, allosteric potentiators and inhibitors that also bind within the δ subunit helix bundle and at subunit interfaces.

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Section: Methodsmentioning

confidence: 99%

[³H]Chlorpromazine Photolabeling of the Torpedo Nicotinic Acetylcholine Receptor Identifies Two State-Dependent Binding Sites in the Ion Channel

et al. 2009

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“…or B.P.C. quality, as appropriate, and all were shown by thin-layer chromatography (Korczak-Fabierkiewicz, Kofoed & Lucas, 1965) to contain less than 0.5 % of the corresponding sulphoxide.…”

Section: A T E R I a L S A N D Methodsmentioning

confidence: 99%

The determination of phenothiazine drugs in pharmaceutical preparations by a difference spectrophotometric method

Davidson

1976

Journal of Pharmacy and Pharmacology

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A method is described for the rapid determination of phenothiazine drugs in a wide variety of pharmaceutical preparations. The drugs are determined by a difference spectrophotometric technique based upon the absorbance of the sulphoxide derivative of the drug relative to the absorbance of a solution of the underivatized drug. The sulphoxide derivatives are formed rapidly and quantitatively at room temperature by the addition of a solution of peroxyacetic acid, prepared by the slow reaction of hydrogen peroxide and glacial acetic acid on standing. The difference absorbance of the solutions is proportional to the concentration of the phenothiazine drug in the preparation and is specific for the intact drug in the presence of oxidative and photochemical decomposition products, colouring and flavouring agents, excipients and most co-formulated drugs.

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The Phenothiazines

TOMPSETT¹

1974

Progress in Chemical Toxicology

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Conversion of chlorpromazine sulfoxide to chlorpromazine by use of metals in acid solution

Cited by 4 publications

References 1 publication

[³H]Chlorpromazine Photolabeling of the Torpedo Nicotinic Acetylcholine Receptor Identifies Two State-Dependent Binding Sites in the Ion Channel

[³H]Chlorpromazine Photolabeling of the Torpedo Nicotinic Acetylcholine Receptor Identifies Two State-Dependent Binding Sites in the Ion Channel

The determination of phenothiazine drugs in pharmaceutical preparations by a difference spectrophotometric method

The Phenothiazines

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Conversion of chlorpromazine sulfoxide to chlorpromazine by use of metals in acid solution

Cited by 4 publications

References 1 publication

[3H]Chlorpromazine Photolabeling of the Torpedo Nicotinic Acetylcholine Receptor Identifies Two State-Dependent Binding Sites in the Ion Channel

[3H]Chlorpromazine Photolabeling of the Torpedo Nicotinic Acetylcholine Receptor Identifies Two State-Dependent Binding Sites in the Ion Channel

The determination of phenothiazine drugs in pharmaceutical preparations by a difference spectrophotometric method

The Phenothiazines

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Product

Resources

About

[³H]Chlorpromazine Photolabeling of the Torpedo Nicotinic Acetylcholine Receptor Identifies Two State-Dependent Binding Sites in the Ion Channel

[³H]Chlorpromazine Photolabeling of the Torpedo Nicotinic Acetylcholine Receptor Identifies Two State-Dependent Binding Sites in the Ion Channel