Drugs online research references
J Pharmacol Exp Ther. 1993 Apr;265(1):194-200.
Mechanism of the bradycardia produced in the cat by the anticholinesterase neostigmine.
Backman SB, Bachoo M, Polosa C.
Department of Anesthesia, Royal Victoria Hospital, Montreal, Quebec, Canada.
Neostigmine evoked bradycardia in vagotomized, propranolol-treated cats. Heart rate decreased by 50% with 0.4 +/- 0.2 mg/kg (mean +/- S.D.) i.v. of neostigmine. The bradycardia was attenuated after acetylcholine (ACh) depletion in the cardiac parasympathetic pathway suggesting ACh release within this pathway was involved. The bradycardia was unchanged after preganglionic terminal degeneration suggesting ACh release was from cardiac ganglion cells. Edrophonium produced a much weaker bradycardia suggesting the anticholinesterase effect of neostigmine may not produce the bradycardia. The neostigmine-induced bradycardia was blocked by systemic atropine (ED50, 0.005 +/- 0.001 mg/kg), pancuronium bromide (ED50, 0.033 +/- 0.021 mg/kg), pirenzepine (ED50, 74.7 +/- 7.9 micrograms/kg), hexamethonium (ED50, 8.3 +/- 1.6 mg/kg) and d-tubocurarine (ED50, 8.6 +/- 3.0 micrograms/kg). The doses of hexamethonium and d-tubocurarine that blocked the neostigmine-induced bradycardia were significantly higher than required for blocking the bradycardia produced by vagus nerve stimulation. Hexamethonium (60 mg/kg i.v.) had no effect on the bradycardia produced by the muscarinic agonist methacholine (100-300 micrograms/kg/min i.v.). The dose of pirenzepine that blocked the neostigmine-induced bradycardia was lower than required for blocking the bradycardia produced by vagus nerve stimulation. McN-A-343 ([4-hydroxy-2-butynyl]-1-trimethyl ammonium m-chlorocarbanilate chloride) (1 mg/kg i.v.) did not produce bradycardia. These observations suggest neostigmine evokes bradycardia by activation of ACh receptors on cardiac ganglion cells producing ACh release and activation of cardiac M2 receptors. The low sensitivity of the neostigmine-induced bradycardia to pirenzepine, and the failure of McN-A-343 to evoke bradycardia, suggest the receptor on cardiac ganglion cells is not an M1-type.(ABSTRACT TRUNCATED AT 250 WORDS)
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8474006&dopt=Abstract
J Pharmacol Exp Ther. 1993 Apr;265(1):401-7.
Specificity of substrate and inhibitor probes for human cytochromes P450 1A1 and 1A2.
Tassaneeyakul W, Birkett DJ, Veronese ME, McManus ME, Tukey RH, Quattrochi LC, Gelboin HV, Miners JO.
Department of Clinical Pharmacology, Flinders Medical Centre, Adelaide, Australia.
Kinetic and inhibitor studies using cDNA-expressed enzymes and human liver microsomes have characterized the specificity of a range of cytochrome P450 (CYP) 1A substrate and inhibitor probes towards the two isoforms comprising this subfamily. Expressed CYP1A1 and CYP1A2 both catalyzed the O-deethylation of phenacetin, although the apparent Km was about 4-fold lower for CYP1A2 (25 vs. 108 microM). Phenacetin O-deethylation exhibited biphasic kinetics in human liver microsomes, and the apparent Km for the high-affinity component (9 +/- 6 microM) was consistent with the involvement of CYP1A2 in this reaction. The prototypic CYP1A xenobiotic inhibitor and substrate probes alpha-naphthoflavone, ellipticine, 7-ethoxycoumarin and 7-ethoxyresorufin all inhibited CYP1A1- and CYP1A2-mediated phenacetin O-deethylation as well as the high-affinity component of human liver phenacetin O-deethylase activity. alpha-Naphthoflavone and 7-ethoxycoumarin were, however, approximately 10-fold more potent as inhibitors of CYP1A2 than CYP1A1. Other putative human CYP1A xenobiotic substrates and inhibitors, including caffeine, 5- and 8-methoxypsoralen, nifedipine, paraxanthine, propranolol and theophylline similarly inhibited CYP1A1- and 1A2-catalyzed phenacetin O-deethylation and the high-affinity human liver phenacetin O-deethylase. In contrast, the monoclonal antibody MAb 1-7-1, raised against 3-methylcholanthrene-inducible rat cytochromes 450, almost abolished CYP1A1-mediated phenacetin O-deethylation, but had no effect on human liver microsomal- or CYP1A2-catalyzed phenacetin dealkylation. Together with previous data, the results indicate that the majority of human CYP1A xenobiotic inhibitor and substrate probes are nonspecific in their recognition of CYP1A1 and CYP1A2, although selectivity is apparent for some compounds.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8474022&dopt=Abstract
Am Rev Respir Dis. 1993 May;147(5):1233-8.
Adrenergic modulation of the pulmonary circulation during strenuous exercise in sheep.
Kane DW, Tesauro T, Newman JH.
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.
In paired experiments, we exercised sheep at a constant rate of 4 mph on a treadmill and measured the hemodynamic effects of alpha receptor blockade (phentolamine 5 mg intravenously), beta receptor blockade (propranolol 1 mg intravenously), and combined alpha and beta receptor blockade. Beta blockade increased pulmonary vascular resistance (PVR) at rest and during steady-state exercise compared with control runs. PVR decreased slightly at rest with alpha blockade, but it was not different during exercise from that of control runs. Combined alpha and beta blockade restored PVR to that of control runs, showing that the vasoconstrictor effect of beta blockade was due to unopposed alpha receptor activation. In all sheep an early rapid decrease in PVR within the first 20 s of the onset of exercise was followed by a smaller, slower change over the next 40 to 240 s. The early decrease in PVR was unaffected by either alpha or beta receptor blockade, suggesting that it was due to recruitment of nonmuscular microvessels. We conclude that alpha and beta receptor activation occurs during exercise but that the net vasoactive effect is neutral. The changes in PVR during normal exercise are a combination of rapid recruitment of microvessels followed by slower vasodilation of resistance vessels.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8484636&dopt=Abstract
Herbs and Pharmaceuticals Online ||
Hair Million herbal formula for hair loss and hair growth ||
Wellstreet online pharmacy for click-order prescription medications ||
Altace Online Pharmacy ||
Rx Drugs USA, Prescription Drugs Online Pharmacy ||
Insurance plans and information ||
Insurance policies for all purposes ||
Antibiotics and prescription medications online literature ||