Symmetric hydrogen bonding in dimethylammonium hydrogen diphenyldiphosphonate.

In the title compound, C2H8N+.C12H11O5P2-, pairs of hydrogen diphenyldiphosphonate anions form dimers across a twofold axis, with two symmetric O...H...O hydrogen bonds [O...O = 2.406 (3) and 2.418 (3) A]. The 12-membered ring thus formed has crystallographic 2 and quasi-222 symmetry. Cations on either side of the ring form N-H...O hydrogen bonds to the four extraannular O atoms, with N...O distances of 2.765 (2) and 2.748 (3) A.

Verofylline, a methylxanthine bronchodilator, in asthma.

Verofylline, a long-acting polysubstituted methylxanthine bronchodilator, was taken orally by eight adult patients with asthma in a double-blind, crossover tolerance study. Peak expiratory flow, forced vital capacity, and its subdivisions were measured weekly 2, 4, and 6 hr after oral dosing with drug or placebo. Peak drug activity developed between 4 and 6 hr after dosing. Subject tolerance was good at the doses used. Dose-response curves for mean forced expiratory volume in one second, peak expiratory flow rate, and forced expiratory flow at the end of 4 hr were greater after 0.05 mg/kg verofylline than after placebo or higher doses of verofylline. Mean percent change in forced vital capacity remained increased as long as 6 hr after 0.15 mg/kg active drug. Verofylline was not very effective as a bronchodilator at the doses used.

Effects of lithium chloride, desmethylimipramine and cocaine on the cardiovascular actions of ouabain in dogs with or without carotid and aortic baro-receptor reflexes.

The cardiovascular effects of ouabain as modified by LiCl, DMI and cocaine in anesthetized dogs with or without buffer nerves (carotid sinus and vagus nerves) were compared. Ouabain significantly increased the LV dp/dt in saline and cocaine but not in LiCl or DMI treated buffered animals. Significant ouabain-induced increase in MAP and decrease in HR were also observed in animals receiving DMI and cocaine. Neither the AD nor the LD of ouabain was modified by Licl or cocaine. DMI, while reducing the AD could not modify the LD of ouabain. In animals without the baro-reflex mechanism (debuffered), significant increase in both LVP and LV dp/dt were observed with ouabain following LiCl and DMI administration. Debuffering itself reduced the LD ouabain in saline treated animals. It was concluded that depending on the presence or absence of baro-reflex mechanism, lithium and DMI could either inhibit or facilitate the inotropic effect of ouabain. Cocaine did not interfere with the actions of ouabain. Ouabain-induced cardiotoxicites were not greatly modified by any of the drugs used.

Effects of microinjection of ouabain into the hypothalamus in cats.

1. In cats anaesthetized with chloralose, repeated injections of 20 mug ouabain were made either into the cerebral ventricles, or into the ventromedial nucleus of the hypothalamus (VMH), or intravenously whilst the electrocardiogram, arterial blood pressure and respiration were recorded.2. The injections produced cardiac arrhythmias preceded by sinus bradycardia, variable changes in arterial blood pressure and respiratory depression. Death occurred either from ventricular fibrillation or from cardiac arrest.3. The arrhythmias which occurred after the injections into the cerebral ventricles were not peripheral effects produced after absorption of the ouabain into the blood stream, because with intravenous injections larger amounts were required to produce the arrhythmias and to cause death than with intraventricular injections. The arrhythmias which resulted in death were due to an action on the VMH. With microinjections of ouabain into this region of the brain death occurred earlier and after smaller doses than after intraventricular injections.4. While sinus bradycardia was abolished by bilateral vagotomy other cardiac arrhythmias were prevented by acute cardiac sympathectomy and cervical cord transection. Thus both the sympathetic and parasympathetic nervous systems appear to be involved in the production of these arrhythmias.5. Since some of the cardiac arrhythmias obtained with ouabain in anaesthetized cats resemble the cardiotoxic effects seen in clinical practice during treatment with digitalis glycosides it is concluded that these effects, too, are, at least in part, central in origin, caused by an action on the VMH and mediated mainly via the sympathetic nervous system.