ABSTRACT
1. The effects of the putative gap junction uncoupler, 1-heptanol, on the neurogenic and myogenic contractile responses of guinea-pig vas deferens were studied in vitro. 2. Superfusion of 2.0 mM heptanol for 20-30 min produced the following reversible changes in the biphasic neurogenic contractile response (8 trials): (i) suppression of both phases; (ii) delayed development of both the first as well as the second phase, accompanied by complete temporal separation of the two phases; (iii) prominent oscillations of force during the second (noradrenergic) phase only. 3. To eliminate prejunctional effects of heptanol, myogenic contractions were evoked by field stimulation of the vas in the presence of suramin (200 microM) and prazosin (1 microM). Heptanol (2.0 mM) abolished these contractions reversibly. 4. These results show that (i) heptanol inhibits both excitatory junction potential (EJP)-dependent and non EJP-dependent contractions of the vas; (ii) a postjunctional site of action of heptanol, probably intercellular uncoupling of smooth muscle cells, contributes to the inhibition of contraction.
Subject(s)
Heptanol/pharmacology , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Vas Deferens/drug effects , Adenosine Triphosphate/pharmacology , Adrenergic alpha-Agonists/pharmacology , Adrenergic alpha-Antagonists/pharmacology , Animals , Electric Stimulation , Guinea Pigs , Hypogastric Plexus/drug effects , Hypogastric Plexus/physiology , In Vitro Techniques , Male , Muscle, Smooth/innervation , Norepinephrine/pharmacology , Prazosin/pharmacology , Purinergic P2 Receptor Antagonists , Suramin/pharmacology , Vas Deferens/innervation , Vas Deferens/physiologyABSTRACT
Various liposomal amphotericin-B formulations prepared from soya phosphatidylcholine and cholesterol were tested for toxicity, therapeutic efficacy and stability in mice infected with Aspergillus fumigatus. No advantage was noted by removing the unencapsulated drug from that bound to liposomes, as evident by the LD50 and efficacy being similar with both dialyzed and undialyzed formulations. Small unilamellar liposomes were more effective and less toxic, but also less stable, as compared to multilamellar vesicles. In view of these results, multilamellar liposomes were prepared without removing the unencapsulated drug and converted to unilamellar vesicles just prior to administration. The LD50 and efficacy of this formulation was similar to freshly prepared small unilamellar liposomes. These liposomes were prepared under aseptic conditions and were found to be sterile and pyrogen-free. The batch-to-batch variation was also found to be quite low, and therefore liposomal amphotericin B formulation suitable for administration in patients suffering with systemic fungal infection has been developed.
