Synthesis and receptor affinities of new 3-quinuclidinyl alpha-heteroaryl-alpha-aryl-alpha-hydroxyacetates.

Five analogues of 3-quinuclidinyl benzilate were prepared in which one phenyl ring was substituted by a heterocycle; a bromine was included on either the remaining phenyl or the heterocycle to provide information relating to the affinity of potential radiohalogenated derivatives. Their affinities for the muscarinic cholinergic receptor were determined. Replacing a phenyl ring with either the 2- or 3-furyl moiety or the 2- or 3-thienyl moiety did not significantly alter the affinity to the muscarinic receptor compared with 3-quinuclidinyl 4-bromobenzilate.

Synthesis and muscarinic cholinergic receptor affinities of 3-quinuclidinyl alpha-(alkoxyalkyl)-alpha-aryl-alpha-hydroxyacetates.

Seven analogues of 3-quinuclidinyl benzilate (QNB) in which one phenyl ring was replaced by an alkoxyalkyl moiety were synthesized and their affinities for the muscarinic cholinergic receptor determined. An oxygen in the beta-position of the moiety was not well-tolerated. By contrast, an oxygen in the gamma-position did not change the affinity for the muscarinic receptor.

Muscarinic receptor subtype selectivity of novel heterocyclic QNB analogues.

In an effort at synthesizing centrally-active subtype-selective antimuscarinic agents, we derivatized QNB (quinuclidinyl benzilate), a potent muscarinic antagonist, by replacing one of the phenyl groups with less lipophilic heterocyclic moieties. The displacement of [3H]-N-methyl scopolamine binding by these novel compounds to membranes from cells expressing m1-m4 receptor subtypes was determined. Most of the novel 4-bromo-QNB analogues were potent and slightly selective for m1 receptors.

Preparation and properties of (R)-(-)-1-azabicyclo[2.2.2]oct-3-yl- (R)-(+)-alpha-hydroxy-alpha-(4-[125I]iodophenyl)-alpha-phenyl acetate and (R)-(-)-1-azabicyclo[2.2.2]oct-3-yl-(S)-(-)-alpha-hydroxy-alpha- (4-[125I]iodophenyl)-alpha-phenyl acetate as potential radiopharmaceuticals.

rac-4-Nitrobenzilic acid was synthesized and resolved with quinidine and quinine to give the corresponding (R)- and (S)-salts. The resolved diastereomeric salts were converted to (R)- and (S)-4-nitrobenzilic acids and subsequent esterification gave their corresponding ethyl esters. Transesterification with (R)-(-)-3-quinuclidinol afforded (R)-(-)-1-azabicyclo[2.

In vitro and in vivo characteristics of [iodine-125] 3-(R)-quinuclidinyl (S)-4-iodobenzilate.

The radioiodinated muscarinic acetylcholine receptor antagonist, [125I] 3-quinuclidinyl 4-iodobenzilate, has two high affinity diastereomeric forms, the (R,R) and (R,S)-isomers. The (R,S)-diastereomer is only threefold lower in affinity than the (R,R)-isomer, but the kinetic properties are considerably different--the dissociation rate constant is 13-fold faster for the (R,S)-isomer and the association rate constant is two to threefold faster. The calculated affinity is therefore only fourfold lower.

[Ambulatory anesthesia in intravenous digital angiography in children. 340 cases].

Immobility in intravenous digital angiography (ANIV) plays a leading part for high-quality results. Three hundred forty children (mean age 30 months, mean weight 12 kg) had an intravenous digital angiography in day-hospital's conditions. Intravenous general anesthesia with or without short neuromuscular blockade is able to help immobility in children.

[Beta-interferon for labial and genital herpes virus infection].

19 women and 9 men, aged 15-59 (mean, 35.1), who had had recurrent lip or genital infections with herpes virus (HSV) for from 1-38 years, were treated with beta-interferon gel (100,000 IU/g), self-administered 4 times daily to the affected areas. In half the patients the drug and a placebo were given in a double-blind, cross-over study.

Placebo-controlled trial of topical interferon in labial and genital herpes.

The efficacy of topical interferon-beta (IFN-beta) treatment was assessed in 25 patients with herpes of the lips or genitals who completed a 2-year follow-up in a double-blind placebo-controlled trial. IFN-beta gel (10(5) U/g) 4 times daily (about 2 x 10(4) U) applied locally during eruptions (about 10 days) reduced the mean number of recurrences (p less than 0.007) and the duration of eruptions (p less than 0.

Synthesis and structure-activity relationships of new muscarinic antagonists.

In an attempt to develop more selective muscarinic acetylcholine receptor (m-AcChR) antagonists, (R)-1-azabicyclo[2.2.2]oct-3-yl-thioxanthene-9-carboxylate, (R,S)-thiochromane-4-carboxylate, and (R,S)-chromane-4-carboxylate were synthesized.

Rocky Mountain spotted fever and jaundice. Two consecutive cases acquired in Florida and a review of the literature on this complication.

Rocky mountain spotted fever is increasing in Florida, a state that has had few cases in the past. The typical clinical illness has been well described, but jaundice has been rarely reported. In two patients with illnesses resembling leptospirosis, jaundice appeared on the sixth and ninth day of illness, and peak bilirubin levels were between 7 and 9 mg/100 ml.

Synthesis and antituberculosis activity of thiocarboxamide derivatives of Schiff bases.

Synthesis of some N-(4-thiocarboxamidobenzylidene)arylamines and N-(substituted benzylidene)-p-thiocarboxamidoanilines from various arylaldehydes and arylamines is described. Fourteen representative compounds were tested in vitro on the ground H37RV.

Effect of pretest temperature on aerosol penetration and clearance in donkeys.

Pretest temperature and humidity were correlated with tracheobronchial particle penetration and clearance data from donkeys housed in unheated outdoor facilities and tested after spending 1-2 h in a temperature- and humidity-controlled laboratory. The animals inhaled an inert insoluble radioisotope-labeled monodisperse aerosol for several minutes. Its retention was monitored continuously for 3 h by external gamma detection.

Effects of fluorocarbons 11 and 12 on tracheobronchial particle deposition and clearance in donkeys.

Donkeys were exposed to trichlorofluoromethane (FC11), dichlorodifluoromethane (FC12) and an equivolume mixture of the two to determine their effects on tracheobronchial particle deposition and mucociliary clearance. There was no statistically significant evidence of changes beyond those variations observed in corresponding air control tests.

Antiserum to lymphocytes and procarbazine compared as immunosuppressants in mice.

As an immunosuppressant procarbazine was as potent as an antiserum to lymphocytes in mice. Both agents significantly prolonged survivals of skin allografts by 4 to 6 weeks. At the maximum tolerated dosage, procarbazine suppressed both circulating hemagglutinins to sheep erythrocytes and plaque-forming cells in the spleen.