Sorption of amiodarone to polyvinyl chloride infusion bags and administration sets.

The loss of amiodarone from i.v. admixtures to flexible polyvinyl chloride (PVC) infusion bags and i.v. administration sets was studied. Admixtures containing amiodarone hydrochloride 600 micrograms/mL and either 5% dextrose injection or 0.9% sodium chloride injection were stored at room temperature in glass bottles (both with and without contact of the drug solution with the rubber bottle closure), in flexible PVC bags, or in rigid PVC bottles. After 120 hours, the contents of each flexible PVC bag were emptied and replaced by methanol, which was allowed to remain in the bag for an additional 120 hours and was then analyzed for amiodarone content. To determine availability of amiodarone after infusion through a 1.8-m PVC i.v. administration set, solutions stored in glass containers were run through the set at 0.5 mL/min for 90 minutes. Samples of drug solutions were collected at appropriate intervals and analyzed by a stability-indicating high-performance liquid chromatography (HPLC) assay. Admixtures containing 0.9% sodium chloride injection were not stable; visual incompatibility was evident after 24 hours of storage in glass bottles, and no further testing was performed. In admixtures containing 5% dextrose injection that were stored in 50-mL flexible PVC bags, 60% of the initial amiodarone concentration remained after 120 hours; approximately half of the lost drug was recovered with the methanol. In effluent collected from the PVC administration set, 82% of the initial amiodarone concentration remained. Amiodarone concentrations did not decrease appreciably, after storage in glass or rigid PVC bottles, indicating that drug loss was probably affected by the plasticizer, di-2-ethylhexyl phthalate.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain histamine H1- and H2-receptors and histamine-sensitive adenylate cyclase: effects of antipsychotics and antidepressants.

Several classes of psychoactive compounds have been investigated for their effects on histamine-sensitive adenylate cyclase in cell free preparations from the guinea-pig cerebral cortex. Their inhibitory actions on this enzyme system have been compared with their abilities to displace [3H]pyrilamine and [3H]cimetidine from histamine H1- and H2-receptor sites, respectively. The results of these studies show that compounds which inhibited the histamine-sensitive cyclase were also displacers of either ([3H]pyrilamine or [3H]cimetidine or both 3H]ligands from their binding sites. In spite of the lack of a correlation between binding and cyclase antagonism, it was observed that compounds that displace both ligands showed greater inhibition of the cyclase than those that have affinities for sites labeled by one or the other ligand. It was concluded that antihistamines, the antipsychotics and the antidepressants share a common property through their antagonism of H1-receptors and that may be responsible for their sedative side effect.

Is dopamine antagonism a requisite of neuroleptic activity?

Neuroleptic activity in laboratory animals is characterized by a decrease in locomotor activity, ptosis, catalepsy, antagonism of certain amphetamine-induced responses, and inhibition of a conditioned avoidance response. Neuroleptics have also been shown to be potent antagonists of dopamine (DA), cis-5,6-Dimethoxy-2-methyl-3-[2-(4-phenyl-1-piperazinyl)-ethyl]indoline (DHO) has been shown to possess the above described pharmacological profile. However, in contrast to known neuroleptics, DHO has no effect on DA levels, DA turnover rate or DA-stimulated cyclase; nor did it have an effect on tyrosine hydroxylase activity. In addition, DHO did not antagonize apomorphine-induced gnawing or amphetamine-induced stereotyped behavior, both of which have been reported to be DA-dependent. However, the agent decreased the level of norepinephrine in the forebrain. An attempt is made to demonstrate that the "DA-hypothesis" of schizophrenia may not be valid in all cases, and that the biochemistry of the disease state is very complex.