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  • 1
    Electronic Resource
    Electronic Resource
    Effect of intravenous atropine and methylatropine on heart rate and secretion of saliva in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 233-240 
    Details
    ISSN: 1432-1041
    Keywords: Atropine ; methylatropine ; heart rate ; saliva secretion ; arrhythmia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Intravenous atropine sulphate (0.25, 0.40, 0.75 and 1.50 mg), atropine methylnitrate (0.08, 0.13 and 0.25 mg) and saline were given to 72 healthy medical students. The effects on heart rate and rhythm, systolic and diastolic blood pressure and salivary secretion were studied. Salivation was inhibited by all the doses of the two drugs. There was a clear dose-response relationship and methylatropine was about 3 times as potent as atropine. Heart rate was accelerated by 0.75 and 1.50 mg atropine, and 0.25 mg methylatropine, whereas 0.25 mg atropine and 0.08 and 0.13 mg methylatropine induced bradycardia, which was considered to be due to a peripheral action. It is suggested that the drugs act as partial agonists at muscarinic receptors. No clear effect on blood pressure was seen, except for the highest dose of atropine, after which the diastolic pressure was increased. 20 out of 59 subjects who received anticholinergics developed supra-ventricular arrhythmias; with both drugs periods of nodal rhythm were most common. They appeared shortly after the injection and usually lasted for a few minutes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00567121
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  • 2
    Electronic Resource
    Electronic Resource
    Effect of urinary pH on the disposition of methadone in man (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 337-342 
    Details
    ISSN: 1432-1041
    Keywords: methadone ; pharmacokinetics ; urinary pH ; RBC level ; saliary level ; mass fragmentography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of urinary pH on the acute disposition of methadone in man was studied in five healthy volunteers. A cross-over experiment was performed in each subject. In the first experiment the subjects were treated with ammonium chloride (urinary pH ≈ 5.2) and in the other the urine was made alkaline (pH ≈ 7.8) by treatment with sodium hydrogen carbonate. d, 1-Methadone-HCl 10 mg (M) was administered intramuscularly on each occasion and blood, saliva and urine levels of M were determined by mass fragmentography. Plasma half-lives, volumes of distribution and body clearances of M were calculated in both experiments. The plasma half-lives in the β-phase were 19.5±3.6 h (acidic urine) and 42.1±8.8 h (alkaline urine), respectively (p〈0.001). The volumes of distribution were increased when the pretreatment was changed from ammonium chloride to sodium bicarbonate, namely from 3.51±0.41 l/kg to 5.24±0.83 l/kg (p〈0.01). The body clearance decreased from 134±21 ml/min (acidic) to 91.9±9.1 ml/min (alkaline urine) (p〈0.01). The ration Mplasma/MRBC was about 2.3 and the elimination of M from RBCs was in good agreement with the plasma kinetics of M under both experimental conditions. The salivary levels of M did not reflect the plasma kinetics and considerable variation was seen in the ratio Msaliva/Mplasma (0.26–2.98). Thus, the present experiments demonstrate that pretreatment either with ammonium chloride or bicarbonate had profound effects on both the distribution and elimination kinetics of methadone.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00548403
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  • 3
    Electronic Resource
    Electronic Resource
    Effect of urinary pH on the plasma and urinary kinetics of remoxipride in man (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 359-363 
    Details
    ISSN: 1432-1041
    Keywords: neuroleptics ; remoxipride ; pharmacokinetics ; urinary pH ; healthy volunteers ; overdose ; plasma prolactin ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of urinary pH on the plasma and urinary kinetics of remoxipride in man has been studied in an open crossover trial in ten healthy male volunteers. Ammonium chloride (urinary pH 5.2) and sodium hydrogen carbonate (urinary pH 7.8) were used as pretreatments on two occasions in randomized order. On each occasion remoxipride 50 mg solution was administered orally and plasma and urinary concentrations of the drug were determined by HPLC and plasma prolactin concentrations by RIA. Remoxipride was rapidly distributed in the body according to a one-compartment model. The mean plasma elimination half-life (t1/2) was 3.6 h in the ammonium chloride experiment and 6.2 h in the sodium hydrogen carbonate experiment. The mean plasma clearance of remoxipride was 141 and 89.9 ml·min−1 in the acidic and alkaline conditions, respectively, and the corresponding mean renal clearances were 58.5 ml·min−1 and 11.7 ml·min−1. The urinary excretion of remoxipride up to 72 h after drug administration was 43.1% and 12.3% following acidification and alkalinization, respectively. Remoxipride induced a similar rapid, transient elevation of plasma prolactin under both conditions. Thus, the urinary pH has a marked effect on the elimination kinetics of remoxipride. After an overdose, treatment with ammonium chloride might be valuable in hastening elimination of remoxipride from the body.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558500
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  • 4
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of methadone in methadone maintenance treatment: Characterization of therapeutic failures (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 497-501 
    Details
    ISSN: 1432-1041
    Keywords: methadone ; pharmacokinetics ; steady state ; addiction rehabilitation ; therapeutic failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Deuterated methadone (M-d3) and GC-MS analysis were used to study the steady state pharmacokinetics of methadone (M) in eight patients reported as therapeutic failures in a methadone maintenance treatment programme. The patients were compared to an unselected group of 12 patients stabilized on M for 25 days. During one dosage interval a pulse dose of M-d3 was administered intravenously instead of the oral M-dose (M-d0). The pharmacokinetic parameters, half-life in the β-phase (t1/2β), volume of distribution during the postdistributive phase (Vdβ) and during steady state (Vdss) were determined as well as the body (ClS) and renal (ClR) clearances of M. Pronounced differences in Vdβ and Vdss were found between the two groups. The therapeutic failures had a smaller Vdβ and Vdss 3.09±0.96 l/kg and 2.74±0.96 l/kg vs 4.56±1.00 l/kg and 4.20±0.78 l/kg in the control group. The differences were due to changes between the groups in the volume of the central compartment. Differences between the groups were also found in t1/2β — 24.5±2.6 h in the therapeutic failures and 34.0±7.0 h (p〈0.001) in the comparison group. However, the change in t1/2β was probably a consequence of the change in Vdβ, as the body clearance of M was similar in the two groups — 104±36 ml/min vs 111±36 ml/min. The smaller volume of distribution could lead to unacceptably high fluctuation of M in the central compartment, and withdrawal symptoms during the latter part of the dosage interval. The appropriate treatment of this subgroup of patients on methadone treatment is not to increase the dose but to shorten the dosage interval. Alternatively, a longer-acting opiate, such as 1-α-acetylmethadol (LAAM), may be used.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542117
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  • 5
    Electronic Resource
    Electronic Resource
    SUBNORMAL CSF LEVELS OF NEUROTENSIN IN A SUBGROUP OF SCHIZOPHRENICS AND NORMALIZATION AFTER NEUROLEPTIC TREATMENT (1982)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 400 (1982), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1982.tb31600.x
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  • 6
    Electronic Resource
    Electronic Resource
    Dose-dependent pharmacokinetics of α-methyl-p-tyrosine (α-MT) and comparison of catecholamine turnover rates after two doses of α-MT (1979)
    Springer
    Journal of neural transmission 44 (1979), S. 145-158 
    Details
    ISSN: 1435-1463
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Groups of rats were injected i.p. with 0.407 or 1.02 mmoles/kg of D, L-α-methyl-p-tyrosine methylester HCl (α-MT). The time-courses forα-MT in plasma and brain were followed together with the endogenous brain dopamine (DA) and noradrenaline (NA) contents. The elimination ofα-MT from plasma and brain was markedly delayed after the highα-MT dose compared with the low dose. At 40 hours after the injection of 1.02 mmoles/kg ofα-MT both plasma and brain levels were high, whereas noα-MT could be detected in plasma or brain at 16 hours after the lower dose. The brain catecholamines were decreased to very low values after the higherα-MT dose (DA 14% and NA 10% of controls at 8 and 24 hours respectively). There was no complete recuperation at 40 hours of any of the amines. After the lowerα-MT dose, the DA concentration was back to control levels at 16 hours and NA at 12 hours. Between 16–40 hours after the highα-MT dose a majority of the rats showed prominent signs of sedation, weight loss and dehydration. No such signs were observed in rats receiving 0.407 mmoles/kg. During the first hour after theα-MT injection the declines of DA and NA respectively were almost identical for bothα-MT doses. When the whole time-course (0–8 hours) after the high dose was considered, biphasic declines were obtained for both DA and NA, suggesting at least two different catecholamine pools. However, due to toxic effects after the highα-MT dose, turnover data have to be interpreted with caution.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01253059
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  • 7
    Electronic Resource
    Electronic Resource
    Effects of centrally administered neuropeptide Y (NPY) and NPY13–36 on the brain monoaminergic systems of the rat (1990)
    Springer
    Journal of neural transmission 79 (1990), S. 193-208 
    Details
    ISSN: 1435-1463
    Keywords: Brain monoamines ; intracerebroventricular administration ; neuropeptide Y (NPY) ; NPY13–36 ; rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of centrally administered NPY on the brain monoamine systems were investigated in the rat. Neuropeptide Y (0.2–5.0 nmol), its C-terminal 13–36 amino acid (a.a.) fragment, NPY13–36 (0.4–10.0 nmol), or saline were injected into the right lateral cerebral ventricle of unrestrained rats. After l h the animals were decapitated, and the brains were taken out. Two cortical regions (‘frontal’ and ‘parietal’), the striatum, the hypothalamus, and the brain stem were dissected out. The tissue contents of noradrenaline (NA), dopamine (DA) and serotonin (5-HT), as well as of their major metabolites, 3-methoxy-4-hydroxy-phenylethylené glycol (MHPG), 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxy-indole acetic acid (5-HIAA) were measured. The most consistent finding was a dose-related increase of both DA and DOPAC levels after treatment with NPY. This effect was reproduced by NPY13–36 in cortical tissue, whereas, in the sub-cortical regions, NPY13–36 only reproduced the effects of NPY on the DOPAC levels. Less consistent effects were found on the NA systems, in which NA levels showed a tendency to increase following low, and decrease after high doses of NPY. These effects were largely reproduced by NPY13–36. In addition, NPY increased tissue levels of MHPG in frontal cortical tissue in a dose-related manner. The brain 5-HT systems were not affected.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01245130
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  • 8
    Electronic Resource
    Electronic Resource
    The influence of human corticotropin-releasing hormone on somatostatin secretion in depressed patients and controls (1989)
    Springer
    Journal of neural transmission 75 (1989), S. 111-118 
    Details
    ISSN: 1435-1463
    Keywords: Somatostatin (SRIH) ; corticotropin-releasing hormone (CRH) ; adrenocorticotropin (ACTH) ; cortisol ; depression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Twenty subjects (10 patients with a major depressive episode and 10 individually matched healthy controls) received 100 μg synthetic human corticotropin-releasing hormone (hCRH) as an i.v. bolus dose. Healthy subjects and depressed patients exhibited a significant increase of plasma somatostatin (SRIH) concentrations with no difference between both comparison groups. Compared to controls, depressed patients showed a significant attenuation of corticotropin (ACTH) responses, while cortisol secretion in response to hCRH was normal. No correlations were found among basal plasma concentrations of SRIH, ACTH or cortisol and SRIH, ACTH or cortisol responses following hCRH. These findings are compatible with the hypothesis that hypothalamic-pituitary-adrenal (HPA) hyperactivity in the depressive state may primarily be due to central hypersecretion of CRH and support the view of a hCRH-induced SRIH secretion which is not related to HPA dysfunction associated with major depression.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01677424
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  • 9
    Electronic Resource
    Electronic Resource
    Arginine vasopressin, but not corticotropin releasing factor, is a potent stimulator of adrenocorticotropic hormone following electroconvulsive treatment (1989)
    Springer
    Journal of neural transmission 75 (1989), S. 101-109 
    Details
    ISSN: 1435-1463
    Keywords: Adrenocorticotropic hormone (ACTH) ; arginine vasopressin (AVP) ; corticotropin releasing factor (CRF) ; cortisol ; depression ; electroconvulsive treatment (ECT) ; radioimmunoassay (RIA)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Neuroendocrine responses to the hypothalamic pituitary-adrenal axis following electroconvulsive treatment (ECT) were evaluated in twelve depressed (6 males/6 females) patients. Plasma concentrations of arginine vasopressin (AVP), corticotropin releasing factor (CRF), corticotropin (ACTH), and cortisol were measured using radioimmunological methods at four different ECT occasions. At each occasion plasma samples were taken immediately before ECT, at the recovery of spontaneous breathing and at 10 and 30 minutes after the ECT. No changes were observed in the plasma CRF concentrations. A large and rapid increase in plasma AVP concentrations was seen after the ECTs. This was followed by increased plasma ACTH and plasma cortisol levels. It is generally believed that AVP exerts a modulatory potentiating action on the CRF-induced ACTH release. The present results demonstrate that AVP per se can cause a release of ACTH from the anterior pituitary.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01677423
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  • 10
    Electronic Resource
    Electronic Resource
    Influence of cysteamine and cysteine on open-field behaviour, and on brain concentrations of catecholamines, somatostatin, neuropeptide Y, and corticotropin releasing hormone in the rat (1989)
    Springer
    Journal of neural transmission 78 (1989), S. 209-220 
    Details
    ISSN: 1435-1463
    Keywords: Catecholamines ; corticotropin releasing hormone (CRH) ; cysteamine ; cysteine ; neuropeptide Y (NPY) ; open field behaviour ; rats ; somatostatin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cysteamine (1.95 or 3.90 mM/kg) administered subcutaneously (sc) markedly decreased the open-field activity of the rats, while the structurally related amino acid cysteine had only minor influence. Cysteamine (1.95 or 3.90 mM/kg) reduced the noradrenaline and increased the dopamine and dihydroxyphenyl acetic acid (DOPAC) levels in the hypothalamus. In striatum the drug decreased both the noradrenaline (1.95 or 3.90 mM/kg) and dopamine (3.90 mM/kg) levels without influencing the DOPAC content. Neither the hypothalamic nor the striatal catecholamines are influenced by administration of equimolar doses of cysteine. Cysteamine (1.95 or 3.90 mM/kg) decreased the somatostatin levels both in the hypothalamus and in the striatum without influencing neuropeptide Y (NPY) and corticotropin releasing hormone (CRH) concentrations. Cysteine administered in equimolar doses did not influence the peptide levels in these brain structures. These data suggest that the cysteamine-induced behavioural changes are related to the decrease of brain noradrenaline and somatostatin concentrations. The structurally related amino acid cystein does not influence the behaviour or the central monoaminergic and peptidergic concentrations in the hypothalamus and striatum of rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01249230
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