Drugs online research references
Arch Biochem Biophys. 1997 Jun 15;342(2):322-8.
Inhibition of lung surfactant secretion from alveolar type II cells and annexin II tetramer-mediated membrane fusion by phenothiazines.
Liu L, Tao JQ, Li HL, Zimmerman UJ.
Institute for Environmental Medicine, University of Pennsylvania Medical Center, Philadelphia 19104, USA.
We investigated the effects of phenothiazines on lung surfactant secretion from rat alveolar epithelial type II cells and on annexin II tetramer (Anx IIt)-mediated membrane fusion. Trifluoperazine and promethazine inhibited ATP-stimulated phosphatidylcholine (PC) secretion from type II cells in a dose-dependent manner. Concentrations that cause 50% inhibition (IC50) were approximately 3 and 25 microM for trifluoperazine and promethazine, respectively. Promethazine also inhibited PC secretion of type II cells stimulated by other secretagogues, including calcium ionophore A23187, phorbol 12-myristate 13-acetate, and terbutaline that are known to stimulate PC secretion via different signal transduction pathways. Since we have recently determined that Anx IIt is involved in PC secretion of type II cells, we examined whether phenothiazines influence Anx IIt's activity. Trifluoperazine and promethazine inhibited Anx IIt's ability to aggregate phosphatidylserine (PS) liposomes, to fuse PS/phosphatidylethanolamine (PE) liposomes, and to fuse PS/PE liposomes with lamellar bodies. These results suggest a relationship between lung surfactant secretion and Anx IIt-mediated membrane fusion.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9186494&dopt=Abstract
J Environ Pathol Toxicol Oncol. 1997;16(1):51-9.
Sublethal effects of hexavalent chromium on the body growth rate and liver function enzymes of phenobarbitone-pretreated and promethazine-pretreated rabbits.
Anjum F, Shakoori AR.
Department of Pharmacology, University of Cambridge, England.
Hepatotoxic effects of chromium have been studied on the liver function enzymes of male New Zealand white rabbits, Oryctolagus cuniculus, with and without pretreatment with phenobarbitone (PB) and promethazine (PM). The total body weight was decreased under all experimental conditions. After PB administration (5 mg/kg body wt/day for 5 days), the serum glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), lactate dehydrogenase (LDH), and isocitrate dehydrogenase (ICDH) activities decreased 21%, 65%, 25%, and 37%, respectively, whereas the alkaline phosphatase (AP) activity increased 70%. After PM treatment (5 mg/kg body wt/day for 5 days) the serum GPT was inhibited 73%, whereas LDH activity was increased 37%. The hepatic GPT and AP activities decreased after PB (52% and 31%, respectively), and PM (48% and 44%, respectively) treatments, whereas the activities of LDH and ICDH increased (after PB: 817% and 109%, respectively, and after PM: 136% and 44%, respectively). Potassium dichromate, administered at a dose of 8 mg/kg body wt/day for 5 days, decreased serum GOT (44%), GPT (61%), LDH (63%), and AP (44%) activities. The hepatic GOT, GPT and AP activities were likewise decreased (86%, 51%, and 46%, respectively), whereas hepatic LDH and ICDH activities increased 667% and 193%, respectively. When administered to PB-pretreated animals, the serum GOT and AP activities were decreased (50% and 68%), whereas ICDH was increased (29%). The hepatic GOT, LDH, and ICDH activities increased 79%, 221%, and 130%, respectively. In the PM-pretreated animals, the chromium treatment inhibited the activities of serum GOT (48%), GPT (44%), and LDH (43%). The hepatic GPT, LDH, and ICDH activities increased 90%, 133%, and 52%, respectively.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9256933&dopt=Abstract
Pharmacol Biochem Behav. 1997 Aug;57(4):707-19.
The role of muscarinic cholinergic receptors in the discriminative stimulus properties of clozapine in rats.
Kelley BM, Porter JH.
Department of Psychology, Virginia Commonwealth University, Richmond 23284-2018, USA.
The present study examined the role of muscarinic receptors in the discriminative stimulus properties of clozapine. One group of rats was trained to discriminate the atypical antipsychotic clozapine (CLZ, 5.0 mg/kg, i.p.) from vehicle in a two-lever drug discrimination procedure, and a second group of rats was trained to discriminate the muscarinic cholinergic antagonist scopolamine (SCP, 0.125 mg/kg, i.p.) from saline. Complete cross-generalization was obtained for SCP in the CLZ-trained rats and for CLZ in the SCP-trained rats. The M1 muscarinic antagonist trihexyphenidyl substituted completely for both CLZ and SCP; however, the M2 antagonist BIBN 99 failed to substitute for either CLZ or SCP. In other substitution tests, the tricyclic antidepressant amitriptyline, the antihistamine promethazine, and cyproheptadine (5-hydroxytryptamine [5-HT]2A/5-HT2C, histamine, and muscarinic antagonist) substituted completely for CLZ and SCP. The tetracyclic antidepressant mianserin substituted completely in the CLZ-trained rats, but did not substitute for SCP. Compounds that produced partial substitution included the tricyclic antidepressant imipramine, the anxiolytic chlordiazepoxide, and the antipsychotic thioridazine. Other compounds tested only in the CLZ-trained rats that failed to produce reliable CLZ-appropriate responding included N-methyl-D-aspartic acid (NMDA, selective agonist for glutamate receptors), metergoline (5-HT2A/5-HT2C antagonist), propranolol (beta noradrenergic antagonist), and phentolamine (alpha noradrenergic antagonist). All of the compounds that produced CLZ-appropriate responding (except for mianserin) display high binding affinities for muscarinic cholinergic receptors. The results of the present study demonstrated that muscarinic receptors (especially M1) play an important role in the mediation of the discriminative stimulus properties of CLZ in rats, and provide additional support for the importance of CLZ's anticholinergic properties as part of it's unique profile as an atypical antipsychotic.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9258998&dopt=Abstract
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