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Biomedical subjects

R Lammintausta

Publications and source records attributed to R Lammintausta.

At least 37 records · Page 2Linked to original sources
PubMed1991

Comparative effects of medetomidine enantiomers on in vitro and in vivo microsomal drug metabolism.

The effects of dexmedetomidine, a selective alpha 2-adrenoceptor agonist, and its levo enantiomer (MPV-1441), on in vitro microsomal P450-dependent drug-metabolizing activities as well as on in vivo aminopyrine elimination and hexobarbital sleeping time were studied. Both enantiomers inhibited the oxidative metabolism of several model substrates and testosterone in rat liver microsomal incubations. Microsomal activities derived from control animals or rats pretreated with phenobarbital were more sensitive to inhibitory effects of dexmedetomidine than those from rats treated with 3-methylcholanthrene. Enzyme activities in human liver microsomes were also inhibited by dexmedetomidine. Retardation of the elimination of aminopyrine was dose-dependent; elimination was marginally retarded with doses up to 100 micrograms/kg (from 17 to 23 min.; both enantiomers). Higher doses of the levo enantiomer prolonged aminopyrine half-life to 78 (1 mg/kg) and 162 min. (10 mg/kg). The hexobarbital sleeping time was prolonged by the dose of 1 mg/kg of the levo enantiomer (128 min. versus 20 min. in controls), while the dose of 0.1 mg/kg had no effect (23 versus 20 min.). These studies indicate that both enantiomers of medetomidine are inhibitors of microsomal drug metabolism in vitro, but significant effects on aminopyrine elimination or hexobarbital sleeping time are apparent only at doses, which do not allow the use of dexmedetomidine because of excessive sedative effect.

Adrenergic alpha-Agonists↗
PubMed1990

Effect of alpha2 antagonists and an agonist on EEG slowing induced by scopolamine and lesion of the nucleus basalis.

In the present study, the effects of an alpha 2 agonist (clonidine, 1.0 mg/kg i.p.) and two antagonists (atipamezole, 1 and 10 mg/kg s.c. and yohimbine, 3.0 mg/kg i.p.) were studied on the EEG activity of naive rats, pretreated with either saline or scopolamine (0.8 mg/kg), or rats receiving lesioning of the nucleus basalis. The alpha 2 antagonists increased fast activity (alpha and beta). Clonidine increased slow wave activity (increased in spectral amplitudes) during periods of immobility and mobility. The EEG slowing, induced by scopolamine, was not alleviated by antipamezole or yohimbine, but in immobile rats, an increase in the delta and theta amplitudes was augmented by clonidine. In nucleus basalis-lesioned rats, the increase in delta activity was partially normalised by the alpha 2 antagonists. The decrease in the beta amplitude, induced by lesioning of the nucleus basalis, was not alleviated with either atipamezole or yohimbine. Clonidine increased the slow wave activity in nucleus basalis-lesioned rats and induced an increase in delta and theta bands during immobility. No changes were induced by clonidine in the EEG recorded from rats with lesions of the nucleus basalis.

Adrenergic alpha-Antagonists↗
PubMed1990

Interaction between the alpha 2-noradrenergic and muscarinic systems in the regulation of neocortical high voltage spindles.

The present experiments were carried out in order to study the interaction between alpha 2-noradrenergic and muscarinic systems in regulating high voltage spindle (HVS) activity in neocortex. Alpha 2-antagonist (atipamezole 1 and 10 mg/kg) blocked HVS activity. Atipamezole at 0.1 mg/kg dose had no effect on HVS activity. Alpha 2-agonist (guanfacine 0.004, 0.02 and 0.1 mg/kg) increased dose dependently HVSs. Guanfacine-induced HVSs were blocked by nucleus reticularis (NRT) lesions and by stimulation of either noradrenergic or cholinergic (pilocarpine) systems. Moreover, combined injections of atipamezole 1 mg/kg and pilocarpine 3 mg blocked HVSs more effectively than either of the drugs alone. Our results suggest that the NRT is jointly modulated by the noradrenergic and cholinergic afferents.

Adrenergic alpha-Antagonists↗
PubMed1989

Medetomidine--a novel alpha 2-adrenoceptor agonist: a review of its pharmacodynamic effects.

1. The pharmacodynamic effects of medetomidine, a novel alpha 2-adrenoceptor agonist, are reviewed. 2. In receptor binding experiments, and in isolated organ preparations medetomidine shows high specificity and selectivity to alpha 2-adrenoceptors. Its alpha 2/alpha 1 selectivity ratio is 1620 compared to 220 of clonidine. It is a highly potent full agonist at alpha 2-adrenoceptors, a fact that also distinguishes it from clonidine. 3. Medetomidine induces a dose-dependent decrease in the central release and turnover of norepinephrine (NE) measured as changes in metabolite concentrations or using pharmacological intervention techniques. 4. The selectivity, specificity and potency of medetomidine is further supported by various in vivo experiments showing dose-dependent hypotensive, bradycardic, sedative, anxiolytic mydriatic, hypothermic and analgesic effects. 5. The pharmacological, neurochemical and behavioral effects of medetomidine can be inhibited by prior, simultaneous or subsequent administration of selective and specific alpha 2-antagonists. 6. In humans medetomidine is well-tolerated and pharmacodynamic effects including e.g. dose-dependent decrease of vigilance, blood pressure, heart rate, salivary secretion and plasma NE are compatible with an agonistic action at alpha 2-adrenoceptors.

Adrenergic alpha-Agonists↗
PubMed1989

Effects of acute administration of medetomidine on the behaviour, temperature and turnover rates of brain biogenic amines in rodents and reversal of these effects by atipamezole.

The effects of acute administration of medetomidine in rodents were examined. Low doses (2.5 micrograms/kg) were anxiolytic, higher doses (10-100 micrograms/kg) sedating, and above 100 micrograms/kg medetomidine treated rats lost their righting reflex and were hypothermic. These higher doses of medetomidine inhibited the release of noradrenaline (NA), dopamine and serotonin in the central nervous system, inhibition of NA release being the most sensitive to medetomidine. All the above effects could be antagonized by administration of suitable doses of the alpha 2-antagonist, atipamezole, indicating that the actions of medetomidine were mediated via activation of alpha 2-adrenoceptors.

Adrenergic alpha-Agonists↗
PubMed1987

Blood glucose, serum insulin, serum growth hormone and serum glycosylated proteins during two years' oral contraception with low-estrogen combinations.

Body weight, fasting blood glucose (GP) (BFG), serum immunoreactive insulin (IRI), serum growth hormone (GH) and serum glycosylated proteins were longitudinally followed in 2 groups of women during two years' oral contraception. One group (n = 10) received a combination of 0.030 mg ethinylestradiol and 0.150 mg levonorgestrel and the other (n = 10) a combination of 0.030 mg ethinylestradiol and 0.150 mg of desogestrel. There was a significant increase in BFG during the study and the values were still rising, when examined 2 months after discontinuation of the pill. Two subjects, reaching the level of 5.5 mmol/l showed normal pretreatment values, when investigated one year later. After 6 months' use of either preparation, GH significantly increased, remained on that level throughout the study and returned to the pretreatment level after discontinuation of the pill. Body weight, IRI and GPP did not change significantly during the study.

Blood Glucose↗
PubMed1987

Plasma renin activity, blood pressure and body weight during two years' oral contraception with two different low-estrogen combinations.

Body weight, systolic and diastolic blood pressure and plasma renin activity (PRA) were longitudinally followed in two groups of women during 2 years' oral contraception. One group (n = 10) received a combination of 0.150 mg levonorgestrel plus 0.030 mg ethinyloestradiol and the other (n = 10) a combination of 0.150 mg desogestrel plus 0.030 mg ethinyloestradiol. Three subjects discontinued the study due to relocation. No statistically significant changes occurred in any of the measured parameters.

Blood Pressure↗
PubMed1984

The effect of infused prostaglandin F2 alpha on plasma antidiuretic hormone and renin activity in early human pregnancy.

The effect of infused prostaglandin F2 alpha plasma antidiuretic hormone and renin activity in early pregnancy was investigated in eight women. After infusion for one and three hours (infusion speed 50 micrograms/min) the PRA had decreased significantly. During the same time the blood pressure also showed a decreasing tendency. No changes were found in plasma vasopressin concentration.

Blood Pressure↗
PubMed1983

Human growth hormone and dopaminergic drugs, with special reference to deprenyl (selegiline): a summary of studies on volunteers.

The tubero-infundibular dopaminergic tract of the hypothalamus has a stimulatory effect on growth hormone (GH) secretion. In healthy volunteers levodopa, through the released dopamine and direct dopamine receptor agonists, therefore induces transient GH secretion. The indirect effect of levodopa at the presynaptic level can be modulated by inhibitory GABAergic drugs and by the potentiating deprenyl, for example. The GH response to direct postsynaptic dopamine receptor agonists like apomorphine is unaffected by these modulators. Below the dopamine level, the inhibitory effect of somatostatin and the negative feedback of the GH itself come into play. These regulatory mechanisms place limitations on dopamine-GH studies in man.

Apomorphine↗
PubMed1982

Transfer of propranolol and sotalol across the human placenta. Their effect on maternal and fetal plasma renin activity.

Eighty milligrams of propranolol or sotalol was administered orally to two groups of 8 parturients who were to undergo elective cesarean section. This was performed 3 hours after drug administration. The transplacental passage of both drugs was registered in each patient. The maternal concentration of propranolol was approximately four times that in the umbilical circulation, while the sotalol level in maternal circulation was twice that in the umbilical circulation. The administration of beta-adrenoceptor antagonists caused a significant decrease in maternal plasma renin activity. After these doses of beta blockers, no difference in the plasma renin activity was found in the umbilical circulation, when compared with the previous normal values at cesarean section.

Adult↗
PubMed1982

Changes in hormonal excretion and urinary flow rate during CPPV and CPAP in healthy volunteers.

In healthy volunteers plasma antidiuretic hormone level, renin activity, and human growth hormone level remained unchanged during successive CPPV, CPAP, and control periods. The plasma level of insulin C-peptide was higher during CPPV than during the control period. Urine flow, glomerular filtration rate, free water clearance, and sodium excretion rate were lower during CPPV than during the successive CPAP and control periods. The renal function changes during CPPV may be a consequence of diminished cardiac output.

Adult↗
PubMed1982

Disopyramide concentrations in saliva.

The saliva and plasma concentrations of disopyramide and its main metabolite, mono-N-dealkyldisopyramide, and the protein binding of disopyramide were studied in ten healthy volunteers after a single oral 400-mg dose of disopyramide. Disopyramide had a concentration-dependent inhibitory effect on the salivary flow rate. The correlations between the salivary and total plasma concentrations of disopyramide (r = 0.774 linear, 0.890 exponential, p less than 0.0001), of the metabolite (r - 0.700, p less than 0.001), and between the salivary and free plasma concentrations of disopyramide (r = 0.785, p less than 0.001) were relatively good. The fraction of disopyramide not bound to plasma proteins varied from not measurable to 0.35, was concentration-dependent, and showed intersubject variation. The ratio of disopyramide concentrations in saliva and plasma (S/P ratio) varied from 0.08 to 1.51 and was highest when the salivary and plasma levels were high. No significant correlation existed between S/P ratio and salivary pH, and the correlation was poor (r = 0.546) between the measured salivary concentrations and those calculated theoretically. A wide interindividual variation was seen in all parameters measured. The salivary concentrations of disopyramide are unreliable for predicting the corresponding total or free plasma concentrations.

Adult↗
PubMed1982

Bilateral oophorectomy and plasma renin substrate concentration.

Plasma renin substrate concentration was studied in 11 premenopausal women subjected to bilateral oophorectomy and hysterectomy. Preoperative plasma renin substrate concentration was 1573 +/- 477 ng angiotensin I/ml (mean +/- SD). Plasma renin substrate concentration did not change significantly after operation (1632 +/- 459 ng angiotensin I/ml) or after 3 months of postoperative estradiol valerate treatment (2 mg/day) (1762 +2- 467 ng angiotensin I/ml). It is concluded that non-pregnant levels of endogenous estrogens are of no significance in the regulation of plasma renin substrate.

Angiotensinogen↗
PubMed1981

Effects of L-deprenyl on human growth hormone secretion.

The effects of L-deprenyl on L-dopa-, apomorphine- and L-tryptophan-induced growth hormone (GH) secretion were studied in thirteen healthy male volunteers. An acute 10 mg dose of L-deprenyl did not stimulate the basal GH secretion. Short-term L-deprenyl premedication significantly enhanced the L-dopa-stimulated GH release. In contrast, L-deprenyl premedication did not change the GH response to apomorphine or L-tryptophan. Potentiation of L-dopa-induced GH release by L-deprenyl indicates an increased availability of dopamine at the receptor level without a direct agonistic effect by the drug. Furthermore, L-deprenyl does not change the function of postsynaptic dopamine receptors involved in human GH release.

Adult↗
PubMed1981

Blood glucose, insulin, antidiuretic hormone and renin activity response during caesarean section performed under general anaesthesia or epidural analgesia.

Glucose loading caused a significant increase in insulin response (IRI) in patients undergoing caesarean section both under general anaesthesia and under epidural analgesia. After a fast intravenous glucose loading given just before the administration of epidural bupivacaine, similar but more variable serum immunoreactive insulin levels were found as compared with those determined after a slower intravenous glucose infusion in patients under general anaesthesia. Plasma renin activity values did not change significantly in either group, but, differing from general anaesthesia, antidiuretic hormone levels (ADH) increased significantly in patients under epidural analgesia. The changes in IRI and ADH response may be caused by a higher psychic stress reaction of the conscious patients during caesarean section under epidural analgesia.

Adult↗
PubMed1981

Effect of medroxyprogesterone acetate and d-norgestrel on plasma renin activity, antidiuretic hormone, and urinary aldosterone in postmenopausal women.

The effect of intramuscular injection of 1,000 mg medroxyprogesterone acetate on plasma renin activity and antidiuretic hormone was studied in 9 postmenopausal women. There were no significant differences in the plasma renin activity and antidiuretic hormone values before and after the injection. 8 postmenopausal women received d-norgestrel (0.18 mg/day) during a 3-week period. The therapy had no effect on plasma renin activity, antidiuretic hormone, or aldosterone excretion.

Aged↗