Biomedical subjects

H Scheinin

Publications and source records attributed to H Scheinin.

87 records · Page 5Linked to original sources

PubMed1988

Acute effects of medetomidine, a selective alpha 2-adrenoceptor agonist, on anterior pituitary hormone and cortisol secretion in man.

Single iv doses (25, 50 and 100 micrograms) of medetomidine, a selective alpha 2-adrenoceptor agonist of the imidazole type, were administered to 8 healthy male volunteers in a randomized, double-blind, placebo-controlled study. The concentration of hGH in plasma was powerfully and dose-dependently increased. The plasma level of cortisol was dose-dependently decreased, whereas TSH showed a slight but statistically significant increase. Plasma levels of PRL, FSH and LH were unaffected by the drug. Medetomidine appears to resemble other alpha 2-adrenoceptor agonists, notably clonidine, in its endocrine effects. Its high selectivity and short duration of action make it a suitable tool for studies of the physiology and pharmacology of alpha 2-adrenoceptors in man.

Adrenergic alpha-Agonists↗

PubMed1987

Noradrenergic and dopaminergic effects of nomifensine in healthy volunteers.

Intravenous doses (100 mg in 20 minutes) of the antidepressant drug nomifensine, administered to male volunteers, increased heart rate and blood pressure, elevated the plasma levels of norepinephrine and its metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), and powerfully stimulated growth hormone release and inhibited the secretion of prolactin. Oral nomifensine, either as a single 100 mg dose or as a similar dose after 2 weeks' treatment with the drug (150 mg/day), caused none of the above effects. This was in line with the limited (less than 30%) oral bioavailability of the active, unconjugated form of the drug, estimated in the same subjects. MHPG in plasma was slightly but consistently reduced by the 2 weeks' treatment, suggesting reduced turnover of norepinephrine. The observed clinical effects of nomifensine are compatible with uptake inhibition and augmented release of norepinephrine and dopamine and possibly direct agonistic effects on dopamine receptors. Although nomifensine was withdrawn from the market because of immunologic complications, it serves as a model compound of a new pharmacologic class of antidepressants, devoid of many of the disturbing side effects of the tricyclic drugs.

Adult↗

PubMed1987

Sedative and cardiovascular effects of medetomidine, a novel selective alpha 2-adrenoceptor agonist, in healthy volunteers.

1. Single intravenous doses (25, 50 and 100 micrograms) of medetomidine (MPV-785, an imidazole derivative), a selective alpha 2-adrenoceptor agonist, were administered to eight healthy male volunteers in a double-blind, placebo-controlled study. 2. The following dose-related effects, all of which were compatible with an agonistic action of the drug at alpha 2-adrenoceptors, were noted: reductions of systolic and diastolic blood pressure (maximum 18/11 mm Hg), heart rate (maximum 10 beats min-1), saliva secretion (maximum 84%) and noradrenaline levels in plasma (maximum 70%). 3. Dose-dependent sedation or impairment of vigilance was also observed, both by subjective and objective (critical flicker fusion threshold) assessments, with the highest dose actually inducing sleep in five of the subjects. 4. The observed effects were in general agreement with those previously seen after intravenous administration of the centrally acting antihypertensive alpha 2-adrenoceptor activating drug, clonidine, but of a shorter duration. 5. The relative importance of alpha 2-adrenoceptors located in peripheral tissues and in the central nervous system for the drug's cardiovascular effects could not be determined, but the high lipid solubility of the compound and the rapid onset of sedation are in favour of a major central component. 6. Medetomidine may be a useful tool for the investigation of the physiology and pharmacology of alpha 2-adrenoceptors in man. In addition, the therapeutic and diagnostic uses of the compound should be investigated in pathological conditions related to increased sympathetic neuronal activity.

Adrenergic alpha-Agonists↗

PubMed1987

Meptazinol and pentazocine: plasma catecholamines and other effects in healthy volunteers.

1. This double-blind, random-order study was designed to compare the clinical effects and the plasma catecholamine responses after i.v. administration of meptazinol at doses 0.7 and 1.4 mg kg-1, pentazocine at doses 0.3 and 0.6 mg kg-1 and saline placebo to six healthy volunteers. 2. Mean arterial pressure was not affected by either drug. Heart rate showed slight drug-related changes. Respiratory rate fell slightly with both drugs, but independently of dose. 3. The critical flicker fusion threshold-test and Maddox wing readings could both clearly differentiate active drugs from placebo. Meptazinol caused more nausea and dysphoria as expressed with visual analogue scales. Both analgesics caused short-lived feelings of euphoria. 4. After pentazocine plasma noradrenaline increased almost two-fold in 10-20 min. The effect of meptazinol was slightly smaller, whereas meptazinol caused a pronounced increase in plasma adrenaline concentrations in two of six subjects. Pentazocine had a smaller, but significant effect on plasma adrenaline. 5. We conclude that the effects of meptazinol in healthy volunteers do not differ markedly from those of pentazocine, although it may cause more nausea and dysphoria. The pronounced increase in plasma adrenaline concentrations in two of six subjects calls for caution in its use in patients with cardiac diseases.

Adult↗

PubMed1987

Monoamine metabolite levels in rat CSF: kinetic studies.

The kinetics of monoamine metabolites, 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), in cisternal CSF were determined after monoamine oxidase (MAO) inhibition (pargyline, 100 mg/kg) and tyrosine hydroxylase inhibition (alpha-methyl-p-tyrosine, alpha-MPT, 250 mg/kg) in awake rats. In addition, the possibility of a peripheral contribution to CSF MHPG levels was investigated by infusing large amounts of the metabolite into vena jugularis. Pargyline induced an exponential decrease of CSF MHPG, 5-HIAA and HVA, with respective half-lives of 51, 86 and 46 min. alpha-MPT caused a slower decline of MHPG and HVA, while 5-HIAA was unaffected. Results from the MHPG-infusion experiments indicate minor peripheral contribution to CSF MHPG levels in acute pharmacological studies. The present paper gives further support for the validity of our new animal model in detecting acute changes in central monoaminergic activity.

Animals↗

PubMed1987

Meptazinol and pentazocine: effects on prolactin, growth hormone and vasopressin levels in plasma.

The effects of two partial agonist opioid analgesics, meptazinol (at doses 0.7 and 1.4 mg/kg intravenously) and pentazocine (at doses 0.3 and 0.6 mg/kg), on anterior and posterior pituitary hormone secretion were studied in six normal human volunteers. Both drugs stimulated the secretion of prolactin dose-dependently, as expected. This effect was seen in all subjects, although two of the six subjects reacted more sensitively to both drugs. Plasma growth hormone concentrations were increased only after the higher dose of meptazinol. This was also seen in all subjects suggesting a specific pharmacological effect. Vasopressin (AVP) in plasma was greatly increased (up to 76 pg/ml) in three of the six subjects after the higher dose of meptazinol, but remained on a low level in the other three and after all other drug doses. The increase in AVP occurred only in those individuals who reported nausea after meptazinol. It was concluded that the augmented AVP release following meptazinol administration was likely to be a non-specific response induced by nausea and not an effect mediated by opiate receptors.

Adult↗

PubMed1986

Effects of yohimbine and idazoxan on monoamine metabolites in rat cerebrospinal fluid.

Effects of two alpha 2-adrenoceptor antagonists, idazoxan and yohimbine, on the concentrations of monoamine metabolites in cisternal cerebrospinal fluid (CSF) of freely moving rats were investigated. Both drugs caused a dose-dependent, up to 250% increase in the concentration of 3-methoxy-4-hydroxyphenylglycol (MHPG) in CSF indicating enhanced release, metabolism and turnover of noradrenaline in the central nervous system (CNS). In addition, a similar increase in homovanillic acid (HVA) in CSF was observed, while the level of 5-hydroxyindoleacetic acid was unchanged. The present results demonstrate the usefulness of monitoring drug-induced alterations in noradrenergic activity in the CNS by measurement of free MHPG in repeatedly collected cisternal CSF samples from awake rats. The possibility that the observed increase in the concentration of HVA after the highly specific alpha 2-antagonist idazoxan reflects increased noradrenergic rather than dopaminergic neuronal activity is discussed.

Amines↗

PubMed1986

Comparison of free MHPG in rat cerebrospinal fluid with free and conjugated MHPG in brain tissue: effects of drugs modifying noradrenergic transmission.

The changes of free 3-methoxy-4-hydroxyphenylglycol (MHPG) in cerebrospinal fluid (CSF) were compared with the corresponding alterations of free and conjugated MHPG in rat brain tissue after various pharmacological treatments modifying noradrenergic neurotransmission. In addition, the effects of the drug treatments on the concentration of noradrenaline (NA) in brain were determined. alpha-Methyl-p-tyrosine (an inhibitor of tyrosine hydroxylase) induced decreases in free and conjugated MHPG in CSF and brain; the free species appeared to decline more rapidly. Reserpine caused similar biphasic changes in free MHPG in CSF and brain but the rapid and transient initial increase in MHPG-SO4 was very weak. Pargyline (monoamine oxidase inhibitor) induced a sharp decline in the concentration of free MHPG in brain and CSF while MHPG-SO4 in brain definitely decreased more slowly. Relatively similar time courses were seen for all three MHPG parameters after administration of MPV-1248 (alpha 2-antagonist) and clonidine (alpha 2-agonist) i.e., increases and decreases, respectively. The present results support the validity of monitoring drug-induced acute changes in central turnover of NA by repeated measurements of free MHPG levels in rat cisternal CSF.

Adrenergic alpha-Antagonists↗

PubMed1986

alpha 2-Adrenoceptor agonists decrease free 3-methoxy-4-hydroxyphenylglycol in rat cerebrospinal fluid.

The effects of alpha 2-adrenoceptor agonists on the concentrations of monoamine metabolites in cisternal cerebrospinal fluid (CSF) of freely moving rats were determined. Clonidine and two new imidazole derivatives, detomidine and medetomidine, and diazepam (as a control substance) were administered in sedative doses and the concentrations of unconjugated 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) in CSF were monitored for 48 h. The alpha 2-agonists caused a dose-dependent, statistically significant decrease in the concentration of MHPG in CSF compared to the concentration in animals treated with saline or diazepam. Detomidine caused a statistically significant increase in the concentration of 5-HIAA compared to control treatments. The present results demonstrate the usefulness of monitoring drug-induced alterations in central nervous system (CNS) noradrenergic activity by measuring free MHPG in repeatedly collected cisternal CSF samples from freely moving rats. The alpha 2-agonists reduced the concentration of MHPG in CSF, indicating a decreased release, metabolism and turnover of noradrenaline in the CNS.

Adrenergic alpha-Agonists↗

PubMed1986

Enhanced noradrenergic neuronal activity increases homovanillic acid levels in cerebrospinal fluid.

Idazoxan, a highly specific and selective alpha 2-adrenoceptor antagonist, caused a dose-dependent increase in the concentration of homovanillic acid (HVA) a metabolite of 3,4-dihydroxyphenylethylamine, in cisternal CSF of freely moving rats. This increase in HVA level could be antagonized by the alpha 2-adrenoceptor agonist medetomidine. The increase was directly proportional to the concurrent elevation in level of 3-methoxy-4-hydroxyphenylglycol, a metabolite of noradrenaline, in the CSF of individual rats and followed a similar time course. It is suggested that the HVA level in CSF may be increased under conditions of enhanced noradrenergic activity and that, in such situations, it reflects noradrenergic rather than dopaminergic neuronal activity. Care should be taken, therefore, when changes in central dopaminergic activity are assessed by measurements of HVA level in CSF.

Animals↗

PubMed1985

Repetitive measurement of monoamine metabolite levels in cerebrospinal fluid of conscious rats: effects of reserpine and haloperidol.

A simple high performance liquid chromatographic method with electrochemical detection is described for the simultaneous determination of unconjugated 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), the principal central nervous system (CNS) metabolites of noradrenaline, serotonin and dopamine (DA), respectively, in small samples of cisternal cerebrospinal fluid (CSF) obtained repeatedly from freely moving rats. Amounts of 30-50 microliter of CSF could be collected repeatedly every 30-60 min allowing monitoring of monoamine metabolite concentration levels in CSF under physiological conditions. None of the metabolites showed any clear diurnal variation. A single injection of reserpine caused a prominent elevation in the concentrations of MHPG, 5-HIAA and HVA in CSF. However, after a rapid increase, the concentration of MHPG was decreased by 85% from the control values. Haloperidol caused a 3-fold increase in the concentration of HVA, indicating increased DA turnover in the CNS. The method enables the reliable quantitative determination of three major monoamine metabolites in small samples of CSF from freely moving rats and appears to be a useful tool in the evaluation of the validity of the clinically used research methods of monitoring drug-induced alterations in CNS monoaminergic activity by metabolite measurements in CSF.

Animals↗

PubMed1985

Tofisopam and midazolam: differences in clinical effects and in changes of CSF monoamine metabolites.

The effect of two repeated oral doses of 100 mg tofisopam 15 mg midazolam and placebo on the concentrations of monoamine metabolites (MHPG, 5-HIAA, HVA) in lumbar CSF were studied in general surgical patients operated on under spinal analgesia (n = 12 in each group). Midazolam, but not tofisopam, improved the quality of sleep the night before surgery. Both active agents reduced preoperative anxiety of the patients, but tofisopam was without subjective sedative action. In the placebo group, in contrast to the active drug groups, there was a slight positive correlation between the MHPG concentration and degree of anxiety before surgery. The only significant difference in the monoamine metabolites in lumbar CSF was found in the concentrations of HVA between tofisopam and placebo treated patients. The lower HVA concentrations suggest that the curious 3,4-benzodiazepine derivative, tofisopam, modifies central dopaminergic activity.

Aged↗

PubMedDate not supplied

Comparison of dexmedetomidine and midazolam sedation and antagonism of dexmedetomidine with atipamezole.

STUDY OBJECTIVE: To evaluate the effects of dexmedetomidine, an alpha-2 agonist, as an intravenous sedative drug and the effects of atipamezole, an alpha-2 antagonist, on recovery. DESIGN: Randomized, double-blind study with three parallel groups. An open dose-finding study preceded it to optimize the atipamezole dose. SETTING: Outpatient operating room at the gynecologic and obstetric university hospital in Helsinki, Finland. PATIENTS: Seventy-two healthy women scheduled for legal termination of pregnancy. INTERVENTIONS: Patients were assigned to one of three groups of 24 patients each to receive either dexmedetomidine 2 micrograms/kg and atipamezole 50 micrograms/kg; dexmetomidine 2 micrograms/kg and saline; or midazolam 0.15 mg/kg and saline. In addition to paracervical block, each patient received two different study drugs: study drug 1 was a sedative agent (either dexmedetomidine or midazolam), administered before the procedure. If the sedation was not deep enough and the patient reacted to the procedure, a low dose of propofol was administered. Study drug 2 was a reversing agent or a placebo, administered following the procedure. MEASUREMENTS AND MAIN RESULTS: The mean time to regain consciousness was shorter in the dexmedetomidine-atipamezole and the dexmedetomidine-saline groups compared with the midazolam group. Postoperative sedation, tested both by subjective and objective assessments, decreased more quickly in the dexmedetomidine-atipamezole group compared with the dexmedetomidine-saline and the midazolam groups. CONCLUSION: Atipamezole is an effective antagonist for reversing psychomotor impairment following dexmedetomidine sedation.

Abortion, Induced↗

PubMedDate not supplied

Laser bronchoscopy in palliative treatment of malignant obstructing endobronchial tumors.

This retrospective study investigates the experience of our ENT Department in the palliative treatment of obstructive malignant bronchial tumors with endoscopic laser surgery. 82 laser procedures on 39 patients were performed between January 1988 and December 1993. In 25 cases, a carbon dioxide (CO2) laser and, in 14 cases, a combined CO2-Nd:YAG laser were used. In 60 procedures, more than half of the tumor could be resected with laser. In 22 cases, minor improvement of the bronchial airway was achieved. Subjectively, most of the patients felt improved breathing after surgery and all were ready to undergo repeated treatment if it was offered. Two fatal complications occurred. We conclude that endoscopic laser surgery is a relatively safe treatment modality for palliation of a compromised airway and can offer a better life quality to selected patients, although it also involves the possibility of fatal complications.

Adult↗

PubMedDate not supplied

Effect of age and repeated hyperbaric oxygen treatments on vagal tone.

OBJECTIVES: To evaluate the influence of repeated hyperbaric oxygen (HBO2) exposures and age on vagal response to hyperbaric oxygenation, and to evaluate the timing of changes in vagal activity during the treatments. STUDY DESIGN: Open, controlled, non-randomized study. METHODS: Heart rate variability of 23 patients with chronic osteomyelitis or radionecrosis of the jaw or reconstructive surgery of the facial region was studied during repeated treatments. During each treatment, the patients were exposed to HBO2 at 2.5 ATA and heart rate variability was measured using power spectral analysis before compression, three times at 2.5 ATA and during and after decompression. The patients were grouped according to age (Cut-off point 50 years). Statistical analysis was carried out using analysis of variance for repeated measurements. RESULTS: Repeated exposures did not change vagal response to hyperbaric oxygenation. Vagal activity measured by HF power increased significantly in both age groups during the HBO2 exposures but there were no significant difference between the groups in the response. However, the level of HF power was significantly higher in the subjects under 50 years old. Significant differences between consecutive measurements were related to pressure changes. CONCLUSIONS: Repeated therapeutic HBO2exposures are not causing permanent changes in vagal control of the heart. Vagal responsiveness to hyperbaric hyperoxia is preserved in advanced age.

Adult↗