Search

Berberine (1) is an alkaloid used widely in the treatment of several diseases. However, its physicochemical properties, pharmacokinetics, and metabolism remain unclear, and conflicting data have been reported. In this study, the main physicochemical properties of 1and its metabolites were evaluated, including lipophilicity, solubility, pKa, and albumin binding. A sensitive HPLC-ESIMS/MS method was developed and validated to identify 1and its main metabolites in human plasma. This method was used to quantify their levels in the plasma of healthy volunteers and hypercholesterolemic patients following a single dose and chronic administration, respectively. In both cases, berberrubine (2) was found to be the main metabolite. Surprisingly, 2is more lipophilic than 1, which suggests that this compound tautomerizes to a highly conjugated, electroneutral quinoid structure. This was confirmed by NMR studies. These results indicate that the higher plasma concentration of 2was a consequence of a more efficient intestinal absorption, suggesting that berberrubine is potentially more pharmacologically active than berberine.

Chloramphenicol (CAP) residues were determined in 35 samples of royal jelly. Fourteen samples were collected by Veterinary Border Inspection officials in Milan and Turin and 21 were submitted by private importers to confirm the quality of their product. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for the identification and determination of CAP, according to the isotope dilution approach for the analysis of royal jelly. The presence of chloramphenicol was detected in 29 out of 35 tested samples at concentrations ranging from 0.6 ?g/kg to 28 ?g/kg, with an average content of 6.1 ?g/kg.

A 23-year-old Asian with histamine-reactive asthma complained of recurrent chest tightness, nasal congestion and flushing immediately after drinking minimal amounts of alcoholic beverages. He was extensively studied to determine the possible mechanism of his alcohol-induced respiratory symptoms. Drinking of either beer or 95 percent ethanol in apple juice immediately provoked vasomotor signs and moderately severe bronchospasm (54 percent and 73 percent decreases in specific airway conductance, respectively), which spontaneously improved over 30 minutes and two hours, respectively. Intravenous and inhaled ethanol caused less bronchospasm than observed with oral ethanol, and recovery was rapid. Pretreatment with cromolyn sodium (inhaled or oral) and isoproterenol had no inhibitory effect on the alcohol-induced bronchoconstriction, whereas atropine, acetylsalicylic acid, cyproheptadine, and chlorpheniramine appeared to have a partial inhibitory effect. Approximately 70 percent inhibition was observed after chlorpheniramine. Observations in this patient suggest that the bronchoconstriction induced by alcoholic beverages is related to their ethanol content and may be related to formation or release of one or more bronchoconstrictor and vasoactive compounds, including a stimulant of histamine1-receptors. The route of ethanol administration may also influence the bronchospastic response.

One hundred subjects answered a respiratory questionnaire and underwent a physical examination, tests of pulmonary function, and three radionuclide lung-imaging procedures. The results of the radionuclide procedures were compared with each other and with pulmonary function tests and other diagnostic findings to determine their relative sensitivity for detecting evidence of early obstructive airway disease. Perfusion lung imaging was less sensitive than most of the other diagnostic tests evaluated. The aerosol and xenon lung-imaging procedures revealed abnormalities with approximately the same frequency as each other, but more often than any one group of pulmonary function tests, including spirometric data, maximal expiratory flow-volume curves, alveolar-arterial oxygen gradient, or indices derived from single-breath nitrogen washout. We concluded that xenon and aerosol lung-imaging studies are sensitive and useful screening procedures for detecting evidence of early localized obstructive airway disease and for locating regionalabnormalities in the airways of patients with respiratory disease.

Previous studies of the long-term effects of habitual marijuana smoking on respiratory status and lung function have yielded conflicting results. In the present study, lung function tests obtained in 74 regular marijuana smokers (duration of smoking > two-five years; frequency of smoking three days/week to several times/day) who denied intravenous narcotic drug abuse were compared with similar tests performed in two groups of control subjects. One group consisted of individuals tested in a mobile laboratory who were computer-matched to the marijuana smokers for anthropometric characteristics and quantity and duration of tobacco smoking; the other group was comprised of 41 nonsmokers of marijuana who were tested in the same laboratory as the marijuana smokers. Paired and unpaired tanalyses revealed lower values for specific airway conductance (–0.07 to –0.08 ± 0.02; P < 0.001) in the marijuana smokers compared with either group of control subjects, but no differences in spirometric indices, closing volume or ΔN2 750–1250. When non-tobacco smoking marijuana users (n = 50) were matched with either non-tobacco smoking or tobacco smoking control subjects, significant differences were again noted in specific airway conductance (P < 0.001) but not in spirometric tests, closing volume or ΔN2 750–1250. These results suggest that habitual smoking of marijuana may cause mild, but significant, functional impairment predominantly involving large airways which is not detectable in individuals of the same age who regularly smoke tobacco. The clinical implications of these findings await further study.

Abstract: The acute bronchomotor effect of nabilone, a synthetic cannabinoid compound, was compared to that of terbutaline sulfate and placebo in six healthy and six asthmatic subjects. Bronchodilation following nabilone was intermediate between that of terbutaline and placebo in the healthy subjects but was equivalent to placebo in the asthmatics. We conclude that oral nabilone (2 mg) does not result in significant acute bronchodilation in patients with asthma.

The bronchodilating activity of oral cannabinoids was evaluated in three double-blind experiments that involved the study of dose-response and interactive relationships and the potential development of tolerance. Data indicated that ▵8-tetrahydrocannabinol (▵8-THC), cannabinol (CBN), and cannabidiol (CBD) in maximal doses of 75 mg, 1200 mg, and 1200 mg, respectively, did not induce significant dose-related physiologic effects in experienced marijuana smokers. ▵8-THC (75 mg) was, however, associated with bronchodilation, tachycardia, and peak highs less than that after ▵9-tetrahydrocannabinol (▵9-THC). The combinations of CBN and CBD with low-dose ▵9-THC (5 mg) did not induce significant bronchodilation but did exert interactive effects on heart rate and “high.” A 20-day study of daily ▵9-THC (20 mg), CBN (600 mg), and CBD (1200 mg) did not indicate tolerance or reverse tolerance to any drug. We conclude that ▵9-THC and, to a lesser extent, ▵8-THC, have acute bronchodilator activity but that CBN, CBD, and their combinations do not provide effective bronchodilation. The daily use of ▵9-THC was not associated with clinical tolerance.Clinical Pharmacology and Therapeutics (1984) 35, 26–32; doi:10.1038/clpt.1984.4

Butenafine HCl, a fungicidal agent of the benzylamine class, was applied to the skin of normal volunteers once daily for 14 consecutive days as a 1% cream formulation (Mentax®). The doses used were approximately 2 to 20 times higher than normal therapeutic doses. Systemic exposure to butenafine was monitored by measuring levels of butenafine and selected metabolites in the plasma and urine during and after the exposure period. Plasma levels of butenafine and its M-2 metabolite were low following repeated 20-g or 6-g doses. The highest combined plasma level for butenafine and M-2 was less than 11 ng/ml, and plasma levels were proportional to the dose administered. The total amount of butenafine and three of its metabolites (M-1, M-2 and M-3) in the urine represented a very small fraction of the applied dose (0.004-0.008%). These data suggest that topical administration of Mentax® does not result in appreciable systemic exposure to butenafine.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

A letter to the editor is presented in response to an editorial that urges the architectural profession to practice ethically when working in Asia in the September 1994 issue.