Drugs online research references
Am J Physiol. 1993 Dec;265(6 Pt 1):G1039-44.
Autoregulation of histamine synthesis through H3 receptors in isolated fundic mucosal cells.
Hollande F, Bali JP, Magous R.
Laboratoire de Biochimie des Membranes, Faculte de Pharmacie, Montpellier, France.
Histamine plays an important role in the control of gastric acid secretion by activating H2 receptors located on parietal cells. In gastric mucosa, histamine is stored both in mast cells and in enterochromaffin-like cells, especially in rodents. It has been proposed that histamine may regulate its own synthesis and/or release through receptors pharmacologically distinct from H1- and H2-receptor subtypes. In this article, we studied the regulation by histamine of histidine decarboxylase (HDC) activity (enzyme responsible for the formation of histamine by decarboxylation of L-histidine) in a fraction of isolated rabbit gastric mucosal cells enriched in mucous and endocrine cells. Histamine and (R)-alpha-methylhistamine (H3 receptor agonist) dose dependently inhibited HDC activity with the same potency (mean effective concn: 32.2 +/- 0.7 and 50.5 +/- 3.1 pM, respectively) and efficacy (35 and 36% inhibition, respectively). In contrast, the H2 agonist dimaprit was devoid of effect. The H3 antagonist thioperamide was found to decrease the histamine- or (R)-alpha-methylhistamine-induced inhibition of HDC activity (mean ineffective concn = 28.3 +/- 1.8 and 9.87 +/- 0.8 nM, respectively), whereas H1 (promethazine) and H2 (ranitidine) antagonists were unable to affect HDC activity. Moreover, high concentrations of thioperamide (1-10 microns) increased histamine release from these cells. All these results allowed us to conclude that, in gastric mucosa, histamine downregulates its own synthesis (and perhaps release) through the stimulation of autoreceptors with pharmacological characteristics of H3 receptors. However, the relationship between histamine synthesis and release remains unclear and needs further investigation.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7506493&dopt=Abstract
Naunyn Schmiedebergs Arch Pharmacol. 1994 Feb;349(2):140-4.
Comparison of the effects of eleven histamine H1-receptor antagonists on monoamine turnover in the mouse brain.
Oishi R, Shishido S, Yamori M, Saeki K.
Department of Pharmacology, Okayama University Medical School, Japan.
To compare in vivo effects of eleven compounds of different classes of histamine H1-receptor antagonists (alcoholamines: diphenhydramine, carbinoxamine, and clemastine; ethylenediamines: mepyramine, tripelennamine, and clemizole; alkylamines: triprolidine and chlorpheniramine; piperazines: meclizine and homochlorcyclizine; phenothiazines: promethazine) on neuronal uptake of dopamine (DA), noradrenaline (NA), and 5-hydroxytryptamine (5-HT), the effects on the turnover of these monoamines were examined in the mouse brain, based on the alpha-methyl-p-tyrosine-induced depletion of DA and NA or probenecid-induced accumulation of 5-hydroxyindoleacetic acid. The DA turnover was reduced remarkably by diphenhydramine, tripelennamine, and promethazine, and also significantly by chlorpheniramine, mepyramine, clemizole, and homochlorcyclizine, at doses used in the ordinary animal experiments. The 5-HT turnover was reduced markedly by mepyramine, tripelennamine, and chlorpheniramine. In contrast, the NA turnover was increased by promethazine and homochlorcyclizine, possibly due to their antagonistic effects on alpha-adrenoceptors. These results suggest that (1) the degree of inhibition of the uptake of DA and 5-HT by histamine H1-receptor antagonists is considerably different, (2) most H1-antagonists have little influence on NA uptake and some compounds enhance NA release, and that (3) carbinoxamine, clemastine, triprolidine, and meclizine have comparatively weak influences on monoamine metabolism. These effects on brain monoamine systems may be related to some central actions of histamine H1-receptor antagonists, such as an addiction to these compounds combined with opioids.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7513381&dopt=Abstract
J Pain Symptom Manage. 1995 May;10(4):267-73.
Morphine and the "lytic cocktail" for terminally ill patients in a French general hospital: evidence for an inverse relationship.
Meunier-Cartal J, Souberbielle JC, Boureau F.
Hautes Etudes de Management Hospitalier, Bussy St. Georges, Hopital Necker-Enfants Malades, Paris, France.
Undertreatment of cancer pain with analgesic drugs is still a frequent problem in French hospitals. In the absence of good analgesic practices, the use of a so-called lytic cocktail, which combines a neuroleptic (chlorpromazine), an opioid (meperidine), and an antihistamine (promethazine) has become common during the terminal phase of the disease. The lytic cocktail (LC) has been subsequently denounced as a type of disguised euthanasia. The aim of our study was to examine the prescription of morphine and lytic cocktail for terminally ill patients in a 427-bed French general hospital during a 3-year period (1989-1991) that coincided with the beginning of a pain relief service. The study was performed in two steps: a chart review of the 841 deceased patients during the observation period and an examination of morphine and parenteral promethazine consumption from the hospital pharmacy. Data from both the charts and the pharmacy showed an inverse relationship between these treatments. Morphine consumption increased while LC consumption decreased. The number of deceased patients who received LC were 24.4% in 1989, 19.9% in 1990, and 6.6% in 1991 (P < 0.001 between 1990 and 1991). The number of deceased who received morphine were 13.6% in 1989, 20.6% in 1990, and 23.9% in 1991 (P < 0.01 between 1989 and 1990). During the same period, the annual hospital morphine consumption increased by 191%, and the annual hospital parenteral promethazine consumption decreased by 62.5%. Our results suggest that, when pain is more correctly treated, the use of an inappropriate method of symptom control decreases.(ABSTRACT TRUNCATED AT 250 WORDS)
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7541434&dopt=Abstract
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