Drugs online research references
Toxicon. 1992 Aug;30(8):907-14.
Action of ciguatoxin on human atrial trabeculae.
Lewis RJ, Hoy AW, McGiffin DC.
Southern Fisheries Centre, QDPI, Australia.
This report describes the action of ciguatoxin-1, the major ciguatoxin present in fishes that cause ciguatera, on the contractile activity of human cardiac musculature. Ciguatoxin-1 caused a large, sustained and concentration-dependent positive inotropy in human atrial trabeculae that were obtained during coronary artery bypass surgery from otherwise healthy hearts. Atenolol (a beta 1-adrenoceptor selective antagonist without local anaesthetic-type activity) or low concentrations of tetrodotoxin abolished the positive inotropy caused by ciguatoxin-1, indicating that ciguatoxin-1 stimulated neural elements present in this tissue to release noradrenaline. The positive inotropic action of ciguatoxin-1 did not stem from a significant direct action on myocardial voltage-dependent sodium channels, nor did it stem from significant alpha 1- or beta 2-adrenoreceptor stimulation. Ciguatoxin-1 caused positive inotropy in preparations stimulated at between 0.02 and 2.0 Hz. Mannitol, currently the treatment of choice for ciguatera, did not significantly reverse the positive inotropy induced by ciguatoxin-1 in human atrial trabeculae.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1523682&dopt=Abstract
Int J Neurosci. 1991 May;58(1-2):127-31.
Norepinephrine inhibits human natural killer cell activity in vitro.
Takamoto T, Hori Y, Koga Y, Toshima H, Hara A, Yokoyama MM.
Department of Internal Medicine, Kurume University School of Medicine, Fukuoka, Japan.
The effect of norepinephrine on human NK cell activity was investigated using a flow cytometry assay. NK cell activity was found to be inhibited by direct addition of norepinephrine to lymphocyte/target cell mixtures in a dose-dependent fashion. This inhibitory effect of norepinephrine was blocked by propranolol but not by atenolol. The results suggest that norepinephrine has a negative influence on NK cell activity and that the effect of norepinephrine is mediated via beta 2-adrenoceptors.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1657810&dopt=Abstract
J Pharm Pharmacol. 1978 Mar;30(3):137-47.
A membrane model of the human oral mucosa as derived from buccal absorption performance and physicochemical properties of the beta-blocking drugs atenolol and propranolol.
Schurmann W, Turner P.
The buccal absorption characteristics and physicochemical properties of the beta-adrenoceptor blocking agents propranolol and atenolol have been investigated to evaluate their permeation properties across biological lipid membranes. The dissociation constants, solubilities of free base, and n-heptane partition coefficients show that propranolol in its unionized form is much more lipophilic than atenolol, both drugs being bases with a similar pKa. Buccal absorption was studied under conditions of varying drug concentration, contact time, and pH, and controlled through the use of a non-absorbable marker. The absorption findings are in general agreement with the pH-partition theory. A new compartmental diffusional model that includes membrane storage and a hypothetical "aqueous pH-buffering surfaces system" allowed a more exhaustive interpretation to be made. A method for the estimation of the intrinsic pH and buffer capacity of the postulated surface system from drug pH-absorption data and partition coefficients alone is described. With human oral mucosa the intrinsic pH was near 6.7, and the buffering capacity of the system (expressed as the ratio deltapH/deltapH eff) about 2.86. The method was validated using published absorption data from the rat small intestine. Absorption of unionized drug through pores is shown to be negligible in the buccal absorption situation. The time course of absorption suggests membrane storage of lipophilic compounds; the in vivo partition coefficient of unionized propranolol relative to the mucous membrane could be calculated for the peusdo-steady state of absorption, i.e. the partition equilibrium between mouth content and membrane, to be approximately 776; this value is of the same order as the in vitro partition coefficient for the erythrocyte/plasma system. The lipid biophase of the buccal membrane is estimated semiquantitatively to be of intermediate polarity (epsilon = 3-4).
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=24685&dopt=Abstract
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