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RATIONALE: Although both cocaine and the phencyclidine analog, BTCP, have dopamine (DA) re-uptake blocking properties, under some conditions their behavioral effects can be differentiated. Therefore, we examined whether the discriminative stimulus (DS) effects of BTCP are different from those of cocaine. OBJECTIVES: To compare the effects of monoamine re-uptake blockers, varying in their in vitro potencies as inhibitors of DA, norepinephrine (NE), or serotonin re-uptake, in different groups of rats trained to discriminate either BTCP or cocaine from saline. Additionally, drugs from other pharmacological classes were tested in both groups. Methods: Rats were trained to discriminate either BTCP (5 mg/kg, i.p.) or cocaine (10 mg/kg, i.p.) from saline under a two-lever FR10 drug discrimination procedure. RESULTS: BTCP and cocaine cross-substituted in BTCP- and cocaine-trained rats. The DA re-uptake blockers, mazindol, indatraline, methylphenidate, GBR12909, and GBR12935, occasioned dose-related drug-lever (DL) selection both in cocaine- and in BTCP-trained rats, with potencies that were significantly correlated. In contrast, the NE re-uptake blockers, nisoxetine, desipramine, and nortriptyline, produced higher levels of DL selection in BTCP-trained rats than in cocaine-trained rats, a profile like that reported in low-dose cocaine-trained rats. Drugs from other classes acted similarly in both discriminations. Further, the alpha1-adrenergic antagonist prazosin dose dependently blocked the DS effects of the training dose of BTCP, but not of cocaine. CONCLUSIONS: The results suggest that the DS effects of BTCP are similar to cocaine, and resemble those of a low training dose of cocaine.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10460313&dopt=Abstract
Am J Physiol. 1985 Mar;248(3 Pt 1):G360-8.
Tricyclic antidepressants and acid secretory response of rabbit gastric cells.
Batzri S.
Tricyclic antidepressants have been tested for their effect on the H2-receptor-mediated changes in cAMP, O2 consumption, and acid secretion in mucosal cells isolated from rabbit stomach. Amitriptyline (AMT) inhibited the action of histamine on both cAMP generation and O2 consumption in an apparent competitive fashion without altering these parameters in unstimulated cells. The onset of this inhibition was rapid and the time at which the increases in these functions had reached steady state was not changed. The Schild regression line for AMT was close to unity, and its Ki values for cAMP production or O2 consumption were 0.75 microM AMT. Imipramine and nortriptyline also caused a rightward shift in the dose-response curve of histamine-induced cAMP generation. The inhibitory action of AMT was specific to histamine in that AMT neither altered the effect of isobutylmethylxanthine on cAMP and respiration nor inhibited the increase in respiration caused by carbachol. However, at relatively high concentrations (250-500 microM), AMT inhibited the increase in cAMP caused by 5 and 100 microM prostaglandin E1 and inhibited the increase in respiration caused by both dibutyryl cAMP (DBcAMP) and by the combination of DBcAMP plus carbachol. Antidepressant drugs were also very potent inhibitors of acid formation as measured by [14C]aminopyrine accumulation (Ki, 1 microM). They inhibited acid formation in control cells, in cells stimulated by histamine, carbachol, and DBcAMP, and also the potentiated response to carbachol plus histamine or DBcAMP. The onset of this inhibition was also rapid, and adding 5 microM AMT to the cell suspension either together with histamine or after stimulation by histamine caused a rapid decline in aminopyrine accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2579580&dopt=Abstract
J Forensic Sci. 1999 Sep;44(5):956-62.
The extent of postmortem drug redistribution in a rat model.
Hilberg T, Ripel A, Slordal L, Bjorneboe A, Morland J.
National Institute of Forensic Toxicology, Oslo, Norway.
The aim of this study was to investigate the postmortem redistribution of several drugs in a rat model and to examine if any of the pharmacological properties was related to the extent of this phenomenon. One of the following drugs: phenobarbital (phenobarbitone), acetaminophen (paracetamol), carbamazepine, codeine, verapamil, amphetamine, mianserin, trimeprazine (alimemazine) or chloroquine was administered together with nortriptyline orally to rats 90 min prior to sacrifice. Heart blood was sampled immediately before sacrifice and after 2 h postmortem, as it has previously been shown that this is sufficient time for postmortem concentration changes to occur in heart blood. Blood was also sampled from the clamped abdominal inferior vena cava (representing peripheral blood) and tissue samples were taken from lungs, myocardium, liver, kidney, thigh muscle, forebrain, and vitreous humor together with a specimen from the minced carcass. Drugs were analyzed by high performance liquid or gas chromatography. For phenobarbital, acetaminophen and carbamazepine the postmortem to antemortem blood drug concentration ratios were close to 1.0 and tissue concentrations were low. The postmortem to antemortem heart blood drug concentration ratio for chloroquine (6.9 +/- 1.5) was higher than for nortriptyline (3.5 +/- 0.3), and the remaining drugs (codeine, verapamil, amphetamine, mianserin, and trimeprazine) showed ratios of the same magnitude as nortriptyline. The postmortem to antemortem blood drug concentration ratios for both heart blood and blood from the vena cava and also the lung to antemortem blood drug concentration ratio were closely related to the apparent volume of distribution for the drugs studied (p < 0.001). Accordingly, an apparent volume of distribution of more than 3-4 L/kg is a good predictor that a drug is liable to undergo postmortem redistribution with significant increments in blood levels. The postmortem drug concentration in blood from vena cava was closely related to the antemortem blood level, confirming that among the postmortem samples, the peripheral blood sample was the most representative for the antemortem blood concentration.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10486948&dopt=Abstract
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