Drugs online research references
Jpn J Pharmacol. 1980 Jun;30(3):325-36.
Avoidance enhancement and discriminative response control by anxiolytics with drugs acting on the GABA system.
Oka M, Yamada K, Yoshida K, Shimizu M.
Two types of conditioned behaviors were investigated for the purpose of evaluating anxiolytic drugs. A conditioning procedure used was an active avoidance in poorly-performing mice. Chlordiazepoxide, diazepam, chlorazepate and meprobamate increased the avoidance rate, while chlorpromazine, haloperidol and nortriptyline did not produce such an effect. The effect of diazepam was potentiated by gamma-aminobutyric acid (GABA) and aminoxyacetic acid (AOAA) and antagonized by picrotoxin and thiosemicarbazide, but was influenced little by spiroperidol, alpha-methyltyrosine, phenoxybenzamine and levallorphan. In addition, the effect of other anxiolytics was potentiated by AOAA and antagonized by picrotoxin. Biperiden, methamphetamine, caffeine and morphine also induced an avoidance enhancement, which was not influenced by AOAA. A drug discrimination experiment was also performed using a milk-reinforced two-lever operant method. In the rats trained to discriminate phenobarbital from saline, diazepam produced a dose-related phenobarbital-lever selection, which was potentiated by AOAA and antagonized by picrotoxin. Chlordiazepoxide, chlorazepate and meprobamate also elicited responses on the phenobarbital-lever. On the other hand, haloperidol, nortriptyline, biperiden, methamphetamine, caffeine and morphine produced a saline-lever selection, at the doses tested. These results suggest that, among several drugs tested, the avoidance enhancement and discriminative response control by anxiolytics may be closely linked with the GABA system.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6109035&dopt=Abstract
Pharmacology. 1989;38(3):151-8.
Changes in amitriptyline distribution in rat brain during a 14-day continuous infusion.
Kurata K, Kurachi M, Tanii Y.
Department of Neuropsychiatry, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
The amitriptyline (ATL) distribution in 12 rat brain regions was examined during 2-, 7- and 14-day continuous ATL infusion, starting with 18 mg/kg/day on the first day. The concentration of nortriptyline, a demethylated metabolite of ATL, in brain and serum was very low in comparison with ATL. The brain/serum concentration ratio of ATL and absolute ATL concentration in the brain were lower on the 2nd day than on the other 2 days. On the other hand, the ATL serum level on the 2nd day was higher than on the other 2 days. The ATL distribution in brain was heterogeneous on each of the three days and there were changes with time in its distribution in two brain portions, the anterior basal ganglia and the medulla oblongata + pons.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2727053&dopt=Abstract
Clin Pharmacol Ther. 1986 Sep;40(3):261-7.
Disposition of single oral doses of E-10-hydroxynortriptyline in healthy subjects, with some observations on pharmacodynamic effects.
Bertilsson L, Nordin C, Otani K, Resul B, Scheinin M, Siwers B, Sjoqvist F.
The active and major metabolite of nortriptyline (NT), E-10-hydroxynortriptyline (E-10-OH-NT), was taken orally as the hydrogen maleate in single doses by nine healthy subjects. The doses (10 to 100 mg) were completely absorbed, as shown by the high urinary recovery of 86.1% +/- 9.9%. Of the given dose, 51.2% +/- 8.7% was recovered as conjugated E-10-OH-NT and 23.9% +/- 4.3% was recovered as unchanged compound. The plasma t1/2 of E-10-OH-NT was 8.0 +/- 1.2 hours and total plasma clearance was 47.5 +/- 10.3 L/hr. The rate of elimination varied little between individuals. There was no indication of dose-dependent elimination. The mean apparent volume of distribution was 7.7 +/- 2.1 L/kg. Single oral doses of 50 mg E-10-OH-NT significantly increased the plasma levels of norepinephrine in both the supine and standing positions (P less than 0.01). Pulse rate increased in the standing but not the supine position. These effects might result from inhibition of neuronal uptake of norepinephrine by E-10-OH-NT. Coupled with its low affinity for muscarinic receptors, these kinetic and pharmacodynamic features of E-10-OH-NT call for further phase I studies.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3742932&dopt=Abstract
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