Drugs online research references
Biochem Pharmacol. 1989 Jun 1;38(11):1827-34.
Differential sensitivity of phosphoinositide and cyclic GMP responses to short-term regulation by a muscarinic agonist in mouse neuroblastoma cells. Correlation with down-regulation of cell surface receptors.
Cioffi CL, el-Fakahany EE.
Department of Pharmacology and Toxicology, University of Maryland School of Pharmacy, Baltimore 21201.
Short-term agonist-induced loss of cell surface muscarinic receptors and desensitization of receptor-mediated cyclic GMP (cGMP) formation and phosphoinositide hydrolysis were examined in mouse neuroblastoma cells (clone N1E-115) in suspension. This treatment resulted in a time-dependent reduction of approximately 40% of the specific binding of the hydrophilic antagonist [3H]N-methyl-scopolamine [( 3 H]NMS) with a T 1/2 of down-regulation of 4.83 min. Scatchard analysis revealed that brief exposure to the agonist resulted in a significant reduction in the Bmax with no change in the Kd. Agonist-induced cGMP formation decreased in a similar time-dependent manner with an average T 1/2 of 4.79 min. However, desensitization of muscarinic receptor-stimulated accumulation of inositol phosphates demonstrated a much slower time-course and was accompanied by a reduction in the maximal response with no change in the EC50. In addition, there was rapid partial recovery of cell surface receptors and desensitized cGMP response, with no apparent resensitization of phosphoinositide hydrolysis. Thus, there was a differential rate of short-term desensitization and resensitization of these two muscarinic receptor-mediated responses. Moreover, desensitization of cGMP formation, but not phosphoinositide hydrolysis, closely paralleled loss of cell surface muscarinic receptors.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2544180&dopt=Abstract
Life Sci. 1985 Sep 23;37(12):1145-53.
The discriminative stimulus properties of mepyramine.
White JM.
Rats were trained to discriminate i.p. injections of mepyramine (10.0 mg/kg) from saline. Correct responses on one of the two levers were reinforced with access to a solution of sweetened condensed milk. A level of at least 27 correct responses in the first 30 (90%) was required in consecutive saline and mepyramine training sessions before a test session was conducted. Amongst the antihistamines, mepyramine, tripelennamine and chlorpheniramine all produced dose-related responding on the mepyramine lever, reaching a maximum of over 90% mepyramine-appropriate responses. Both tripelennamine and chlorpheniramine were more potent than the training drug. Diphenhydramine and promethazine produced high levels of mepyramine-appropriate responses, but the 90% level was not reached with any dose tested. The dextrorotatory isomer of chlorpheniramine, which binds with high affinity to H1-receptors, was approximately twice as potent as the racemic mixture. The anticholinergic, scopolamine, and the local anaesthetic, procaine, produced only low levels of mepyramine-appropriate responses. However, 10.0 mg/kg of the anti-depressant imipramine produced over 90% mepyramine-appropriate responses. These results suggest that a discrimination can be formed on the basis of the specific H1-receptor antagonist activity of mepyramine.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2863732&dopt=Abstract
Am J Psychiatry. 1985 Jun;142(6):738-40.
Effects of physostigmine on pulse, blood pressure, and serum epinephrine levels.
Janowsky DS, Risch SC, Huey LY, Kennedy B, Ziegler M.
In this study, the infusion of physostigmine in 14 patients with affective disorder who were pretreated with methscopolamine caused significant and often profound increases in the patients' epinephrine levels, pulse rates, and blood pressure. Since physostigmine is being used experimentally in the treatment of elderly subjects who have Alzheimer's disease, these cardiovascular effects may have clinical importance.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=4003595&dopt=Abstract
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