Drugs online research references
Pharmacol Toxicol. 1997 Dec;81(6):259-64.
Interactions between promazine and antidepressants at the level of cellular distribution.
Daniel WA, Wojcikowski J.
Polish Academy of Sciences, Institute of Pharmacology, Krakow, Poland.
The pharmacokinetic interactions in clinical combinations of a phenothiazine neuroleptic and antidepressants at the level of cellular distribution were investigated. Uptake experiments were performed on slices of various rat tissues as a system with intact lysosomes. Promazine and antidepressants (imipramine, amitriptyline, sertraline, fluoxetine) were incubated separately or jointly with tissue slices for 1 hr. Initial concentration of each drug was 5 microM. The interaction studies were carried out in the absence and presence of ammonium chloride (20 mM), a lysosomotropic compound which increases the internal pH value of lysosomes. All the tissues known for their abundance of lysosomes (the lungs, liver, kidneys) were the site of an interaction between promazine and antidepressants. The neuroleptic and antidepressants mutually inhibited their tissue uptake. The potency of interference of each antidepressant with the lysosomal uptake of promazine was similar. The interactions did not occur in the presence of ammonium chloride, which indicates involvement of the lysosomal trapping. Carbamazepine, a lipophilic but non-lysosomotropic drug, did not interfere with the promazine uptake, and the adipose tissue containing very few lysosomes was never the site of interaction in our experiment. Distribution interactions were also observed in the brain and in some cases in muscles (the tissues less abundant of lysosomes), the effect of the inhibitory drug being usually more potent than that of ammonium chloride. Most of the interactions occurring in these two tissues were also observed in the presence of ammonium chloride. Most of the interactions occurring in these two tissues were also observed in the presence of ammonium chloride, which suggests involvement, at least partially, of a non-lysosomal trapping mechanism. The consequences of the observed distributive interactions at the level of lysosomal trapping in vitro are diminished intralysosomal concentration of the basic lipophilic psychotropic and its increase in cell membranes and fluids. In vivo, a shift from the organs or tissues rich in lysosomes to those less abundant in these organella, and an increase in the free drug concentration in body fluids may be expected. In conclusion, the obtained results show that, regardless of the previously known metabolic interactions between psychotropics, interactions at the levels of cellular and body distribution are also feasible.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9444666&dopt=Abstract
note: kwd match prozac online literature
J Neural Transm. 1997;104(8-9):953-66.
Fluoxetine increases norepinephrine release in rat hypothalamus as measured by tissue levels of MHPG-SO4 and microdialysis in conscious rats.
Perry KW, Fuller RW.
Central Nervous System Research, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA.
The selective serotonin uptake inhibitor fluoxetine (10 mg/kg i.p.) increased tissue levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylethylene glycol sulfate (MHPG-SO4) in rat hypothalamus, indicating an increased release of norepinephrine. Microdialysis studies in conscious rats showed that fluoxetine (10 mg/kg i.p.) increased extracellular concentrations of norepinephrine as well as serotonin in the hypothalamus. In contrast, desipramine (10 mg/kg i.p.) increased extracellular concentration of norepinephrine but not serotonin in the hypothalamus. Consistent with its mechanism of being a selective serotonin uptake inhibitor, local perfusion of fluoxetine (10 microM) caused a 7-fold increase in hypothalamic extracellular serotonin and a small non-significant increase in extracellular norepinephrine. The subsequent systemic injection of fluoxetine (10 mg/kg s.c.) after local perfusion caused a 3-fold increase in extracellular norepinephrine, indicating that fluoxetine's action leading to an increase in extracellular norepinephrine was not occurring in the terminal areas of the hypothalamus but elsewhere in the brain, possibly cell bodies in the locus coeruleus.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9451727&dopt=Abstract
note: kwd match prozac online literature
Brain Res. 1997 Nov 7;774(1-2):94-105.
p-Chlorophenylalanine and fluoxetine inhibit D-fenfluramine-induced Fos expression in the paraventricular nucleus, cingulate cortex and frontal cortex but not in other forebrain and brainstem regions.
Javed A, Van De Kar LD, Gray TS.
Department of Cell Biology, Neurobiology and Anatomy, Loyola University of Chicago School of Medicine, Maywood, IL 60153, USA.
D-Fenfluramine, a putative serotonin releaser and reuptake inhibitor, is commonly prescribed for the treatment of obesity. Brain sites activated by D-fenfluramine have been mapped via the expression of the immediate early gene Fos. However, it is not clear that serotonin release in the brain mediates the effects of D-fenfluramine on Fos expression. The present study determined whether D-fenfluramine induces the expression of Fos in the brain through the release of serotonin. Rats were pretreated either with the serotonin depleting drug p-chlorophenylalanine (PCPA) or with the serotonin reuptake inhibitor fluoxetine. Both drugs inhibited D-fenfluramine-induced Fos expression in the cingulate cortex, frontal cortex, and the parvocellular subdivision of the paraventricular nucleus of the hypothalamus. Neither drug reduced D-fenfluramine-induced Fos responses in several other brain areas, including the caudate-putamen, amygdala, and brainstem regions such as the lateral parabrachial nucleus and nucleus of the solitary tract. These results indicate regional specificity of mechanisms mediating D-fenfluramine-induced Fos expression. It is likely that D-fenfluramine-induced Fos expression at various sites in the brain is mediated via a combination of serotonin release and other, as yet unidentified, neurotransmitters.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9452197&dopt=Abstract
note: kwd match prozac online literature
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