Mechanism of action of 6, 7, 8, 9, 10, 12-hexahydro-azepino-[2, 1-b] quinazolin-12-one-(RLX)--a novel bronchodilator.

The present study presents a mode of action profile of RLX (6, 7, 8, 9, 10, 12-hexahydro-azepino-[2, 1-b]-quinazoline-12-one) a bronchodilator obtained by the chemical modification in the molecule of alkaloid vasicine (Ex: Adhatoda vesica). The effect of RLX (p.o.) was observed on: (a) mast cell degranulation, (b) release of histamine and prostaglandin E (PGE), (c) 45Ca uptake and (d) activities of cAMP phosphodiesterase (PDEase) and lipoxygenase enzymes in mesenteries/peritoneal mast cells/lung tissue homogenates in rats under systemic anaphylaxis. RLX (10 and 20 mg/kg) inhibited antigen-induced mast cell degranulation and released of histamine from target tissues. An increased outflow of PGE (lungs) and an inhibited 45Ca uptake (peritoneal mast cells) were noted. Lung PDEase and lipoxygenase activities were decreased. These results suggested that RLX could be acting like disodium cromoglycate and aminophyline with additional attributes its oral efficacy and long duration of action.

Permeability characteristics of piperine on oral absorption--an active alkaloid from peppers and a bioavailability enhancer.

Piperine, [1-[5-[1,3-benzodioxol-5-yl]-1-oxo-2,4, pentadienyl] piperidine], is a pungent alkaloid present in Piper nigrum Linn, and P. longum Linn. It is shown to enhance the bioavailability of various structurally and therapeutically diverse drugs. A concise mechanism responsible for its bioavailability enhancing action is poorly understood. This study is an effort to understand the absorption dynamics of piperine in intestine on oral absorption. It encompasses intestinal everted sacs as an experimental model. Cycloheximide treatment and exclusion of Na+ salts from incubating medium were the variables used. Absorption half life, absorption rate, absorption clearance and apparent permeability co-efficient were computed from the data. Experiments to denote physico-chemical characteristics of this moiety exhibited that it is a weak base, highly lipophilic in nature with partial solubility in aqueous media. It exhibited passive diffusion constituting non-saturable absorption kinetics. Transport of piperine was not resisted by UWL and was proposed to be absorbed through transcellular pathway. It displayed short absorption clearance and high apparent permeability co-efficient. Data thus obtained suggested that piperine is absorbed very fast across the intestinal barrier. It may act as an apolar molecule and form apolar complex with drugs and solutes. It may modulate membrane dynamics due to its easy partitioning thus helping in efficient permeability across the barriers.

Toxicity studies with potassium embelate, a new analgesic compound.

Potassium embelate, 2,5-dihydroxy, 3-undecyl-1, 4-benzoquinone, from Embelia ribes Burm. was subjected to toxicity evaluation which included subacute, chronic, reproductive toxicity testing and teratological investigations in laboratory animals (mice, rats and monkeys). The results did not indicate adverse effects suggesting that potassium embelate is a safe compound.

Possible interaction of potassium embelate, a putative analgesic agent, with opiate receptors.

The in vivo studies have been carried out in the rat brain for characterization of binding sites for potassium embelate (ex: Embelia ribes) a potent centrally acting analgesic compound. The results indicate that mixed mu and kappa binding sites in the brain may be involved in the analgesic action of this compound.

Effect of quercetin and Albizzia saponins on rat mast cell.

In the present work the effect of quercetin obtained from (Allium cepa). Albizzia lebbek (crude extract of seeds) and a pure saponin fraction of Albizzia has been studied on the mast cells in the mesentery and peritoneal fluid of rats subjected to anaphylaxis. The results show a mast cell membrane stabilizing effect of these test drugs.