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T Fan

Publications and source records attributed to T Fan.

43 records · Page 3Linked to original sources
PubMed1986

Chronic ethanol inhibits rat hippocampal "stimulus-secretion" coupling mechanism for 5-hydroxytryptamine in vitro.

Effects of ethanol on serotonergic neurotransmission were investigated in crude mitochondrial fraction (P2 fraction) from rat brain hippocampus and hypothalamus. The [14C]5-HT preloaded P2 fraction was exposed to 45 mM KCl to induce 5-hydroxytryptamine release in vitro. Ethanol in vitro did not produce any significant inhibition of [14C]5-HT release until its concentration was greater than 100 mM. The K+-evoked 45Ca uptake of hippocampal P2 fraction was unaffected by 100 mM. However, 200 mM ethanol inhibited approximately 63% of K+-evoked 45Ca uptake. Chronic ethanol (10 g/kg/day) for 6 days inhibited [14C]5-HT release from hippocampus whereas it did not affect [14C]5-HT release from hypothalamus. Results indicate that chronic ethanol treatment may decrease serotonergic neurotransmission in selective brain regions. The reduction in 5-hydroxytryptamine release was the result of inhibition in "stimulus-secretion" coupling mechanism.

Alcoholism↗
PubMed1983

Amitriptyline and ethanol: pharmacokinetic and pharmacodynamic interaction.

Amitriptyline has clinically important interactions with ethanol. Five healthy volunteers received 25 mg of amitriptyline orally, preceded by one hour and followed for eight hours by oral ethanol (or juice), dosed to achieve and maintain blood ethanol concentrations of 800 mg/l. In the presence of ethanol, amitriptyline free plasma concentrations were increased by a logarithmic mean of 204%, 186% and 127% at 1.5, 2, and 2.5 h, respectively, and amitriptyline free AUC0-8h was increased by 48% +/- 13% (means +/- SEM) (t = 5.21, p less than 0.01). Nortriptyline total AUC0-8h was increased by 26.6% +/- 12% (means +/- SEM) (t = 2.21, p less than 0.09). At the time of peak amitriptyline plasma concentrations, mean postural sway was increased over baseline by 92% with, and 2% without ethanol; likewise, mean short term memory (word recall) was decreased over baseline by 71% with, and 37% without ethanol. Ethanol increases free amitriptyline plasma concentrations most dramatically during the period of drug absorption; this is due to a decrease in amitriptyline hepatic clearance, resulting in decreased first-pass extraction. Together with the pharmacodynamic interaction, the kinetic changes provide a rationale for the toxicity of this combination and its deleterious effects on psychomotor skills.

Adult↗
PubMed1980

Variability in heparin effect on serum drug binding.

Heparinized saline was given to seven men and one woman, aged 21 to 42 yr, after a 14-hr fasting period and 2 hr after breakfast; blood was collected in nonoheparinized tubes. Diazepam (D alpha) and warfarin (W alpha) free fractions were determined in serum by equilibrium dialysis to which radiolabeled drug was added. After 50 U heparin (Harris LO14) intravenously, the maximum effect on D alpha, W alpha, and free fatty acids (FFA) developed in 5 min and lasted 20 to 30 min. D alpha rose and W alpha fell (p < 0.01) at 5 min. Cumulative doses of heparin increased FFAs (F4,16 = 18.29, p < 0.0005). D alpha rises (r = 0.73, p < 0.001) and W alpha falls (r = -0.74, p < 0.001) correlated with changes in FFAs. D alpha rises and W alpha falls were greater postprandially than in the fasted state (p < 0.01). Five subjects were randomly assigned up to 400 U intravenously of each of two different heparin lots (Harris LO14, and Organon LA39.) The FFA rises (reflecting heparin lipolytic activity, F1,32 = 179.62, p < 0.0005), D alpha rises (F1,32 = 34.22, p < 0.0005), and the W alpha falls (F1,32 = 33.20, p < 0.0005) by heparin Harris LO14 were greater than those by heparin Organon LA39. Although small doses of heparin, such as those in heparin locks, can affect drug binding, the extent and variability of the effect depends on the biologic activity of the heparin, and varies with manufacturer and lot, exact time of sampling, and eating.

Adult↗