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Biomedical subjects

M Scheinin

Publications and source records attributed to M Scheinin.

At least 145 records · Page 8Linked to original sources
PubMed1990

Medetomidine premedication in dental surgery--a double-blind cross-over study with a new alpha 2-adrenoceptor agonist.

A single 50-micrograms dose of medetomidine, a highly selective alpha 2-adrenoceptor agonist, was administered intravenously as premedication 30 min before surgical third molar extraction under local anaesthesia to ten healthy male subjects in a double-blind, placebo-controlled, cross-over study. Blood pressure, heart rate, plasma catecholamines and cortisol were measured as indicators of operation-related stress. Apprehension and pain were assessed with repeated Visual Analogue Scales. The dental surgeon rated the overall effectiveness of the premedications, and the patients reported their subjective preference. Drug-induced sedation was determined with the Critical Flicker Frequency (CFF) test. The dental surgeon rated medetomidine as significantly more effective premedication than saline placebo. Apprehension was significantly reduced by medetomidine. The patients clearly preferred medetomidine premedication. Blood pressure was lower in the medetomidine session, whereas no significant differences were seen in heart rate. Plasma noradrenaline was lower after medetomidine, but adrenaline and cortisol levels were not affected. In conclusion, medetomidine may offer a useful alternative to traditional premedications in out-patient surgery, and its clinical usefulness should also be studied in other anaesthetic paradigms.

Adrenergic alpha-Agonists↗
PubMed1990

Biological correlates of mental stress related to anticipated caesarean section.

The relationships between self-reported assessments of acute anxiety and several biochemical and physiological indicators of stress reaction were investigated in pregnant women at term in connection with spinal analgesia for caesarean section. Fear and apprehension were statistically significantly associated only with blood pressure and with an increase in heart rate from the previous day. The subjective estimate of the quality of the preoperative night's sleep was negatively associated with biochemical plasma and cerebrospinal fluid (CSF) measures of sympatho-adrenal activity. The previously reported negative correlation between body height and 5-hydroxyindoleacetic acid (5-HIAA, an indicator of serotonin metabolism) in lumbar CSF was confirmed. The concentration of 5-HIAA in CSF was positively correlated with the levels of other acidic monoamine metabolites and cortisol in CSF. It is concluded that hormone and monoamine metabolite measurements in CSF and plasma have only limited usefulness as quantitative indicators of the intensity of preoperative fear and anxiety.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Dexmedetomidine premedication for minor gynecologic surgery.

The effects of four different doses (0.167, 0.33, 0.67, and 1.0 microgram/kg) of dexmedetomidine, a novel alpha 2-adrenoceptor agonist, on anesthetic requirements, hemodynamics, and plasma catecholamine levels were investigated in a single-blind fashion in 20 healthy (ASA physical status I) women scheduled for uterine dilatation and curettage. The drug was administered intravenously 15 min before anesthesia induction with thiopental. Nitrous oxide/oxygen (70%/30%) was used for maintenance. Dexmedetomidine was well tolerated, and no serious drug-related subjective side effects or adverse events were observed. The most prominent subjective effects were tiredness and decreased salivation. The total amount of thiopental needed to perform uterine dilatation and curettage was decreased dose-dependently from 400 +/- 166 mg (mean +/- SD) after 0.167 microgram/kg of dexmedetomidine to 180 +/- 65 mg after 1.0 micrograms/kg of dexmedetomidine (P = 0.028). Blood pressure, heart rate, and plasma norepinephrine levels were reduced after dexmedetomidine. The optimal dose of dexmedetomidine for single-dose intravenous premedication studies in minor surgery appears to be in the range of 0.33-0.67 micrograms/kg.

Adrenergic alpha-Agonists↗
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

A comparison of two sedative premedications for minor oral surgery under local anaesthesia.

Two commonly used drug combinations were studied as premedications before surgical 3rd molar removal under local anaesthesia. The study was randomized, crossover and double-blind in 12 patients. Our routine premedication for lengthy operations, consisting of diazepam 10 mg p.o. plus i.m. scopolamine 0.006 mg/kg and morphine 0.2 mg/kg, was compared with a combination of diazepam 10 mg p.o. plus metoprolol 50 mg p.o. The latter combination was expected to cause fewer central nervous system side effects and be more suitable for out-patient surgery. Drug levels in blood, physiological and biochemical indicators of operation-related stress, CNS side effects, and the patients' subjective preferences were monitored. Both combinations were equally accepted by the patients, but the diazepam/scopolamine/morphine combination caused clearly more side effects after discharge than diazepam/metoprolol. The operation-related haemodynamic changes and plasma catecholamine responses were similar after both premedications.

Adult↗
PubMed1989

Effects of dexmedetomidine, a selective alpha 2-adrenoceptor agonist, on hemodynamic control mechanisms.

Dexmedetomidine, a selective alpha 2-adrenoceptor agonist, was administered to five healthy male volunteers in single intravenous doses of 12.5, 25, 50, and 75 micrograms as part of a placebo-controlled study. The drug caused dose-dependent decreases in systolic and diastolic blood pressure. A small initial hypertensive response was observed after injection of the two highest doses. Heart rate was decreased. The concentration of norepinephrine in plasma was decreased significantly (by up to 92%), and the decrease was dose-dependent. No significant drug-induced alterations were observed in plasma renin activity or in the concentrations of atrial natriuretic peptide and arginine vasopressin in plasma. Other drug effects included dose-dependent impairment of vigilance and stimulation of growth hormone secretion. Plasma cortisol levels were unaffected. Dexmedetomidine is a potentially useful tool for studies of the physiology and pharmacology of alpha 2-adrenoceptors in human beings and may have therapeutic applications in clinical conditions in which sedative and sympatholytic effects are considered beneficial, such as premedication for anesthesia and surgery.

Adrenergic alpha-Agonists↗
PubMed1989

Alfentanil obtunds the cardiovascular and sympathoadrenal responses to suxamethonium-facilitated laryngoscopy and intubation.

Alfentanil 75 micrograms kg-1 or saline (control group) was given 1 min before induction of anaesthesia in 20 healthy patients premedicated with diazepam 0.14 mg kg-1 and pethidine 1 mg kg-1. Anaesthesia was induced with a sleep dose of thiopentone preceded by glycopyrrolate. Suxamethonium 1 mg kg-1 was used to facilitate laryngoscopy (which lasted 10 s) and tracheal intubation. Arterial pressure, heart rate and noradrenaline concentration in mixed venous plasma increased significantly after suxamethonium, and increased further after laryngoscopy and intubation in the control group (n = 10). The QT interval of the ECG was prolonged after the administration of suxamethonium, and was prolonged further after laryngoscopy and intubation. All these changes were attenuated in patients pretreated with alfentanil (n = 10), but four patients had chest wall rigidity. Changes in the QT interval correlated directly with the changes in plasma noradrenaline concentration (r = 0.67). Plasma adrenaline concentrations decreased during induction of anaesthesia in both groups.

Adult↗
PubMed1989

Propofol infusion for sedation in outpatient oral surgery. A comparison with diazepam.

An infusion of propofol was compared with intravenous boluses of diazepam as sedation for minor oral surgery under local anaesthesia in 12 healthy patients who had elective bilateral surgical extraction of lower third molars; the patients served as their own controls. Plasma catecholamine, vasopressin and cortisol concentrations were determined from repeated blood samples. The total administered dose of propofol was 3.93 (SD 1.34) mg/kg and of diazepam 0.28 (SD 0.07) mg/kg. No cardiovascular depression or airway problems occurred. Other side effects were also rare but some discomfort on injection was frequent with propofol. Recovery times were faster after propofol than after diazepam as assessed by the Maddox wing and visual analogue scales. Propofol also provided better amnesia compared to diazepam at the time of the extraction of the teeth. Eight of the 12 patients subjectively preferred propofol sedation. There was no hormonal stress response in either group.

Adult↗
PubMed1989

Inhibition of monoamine oxidase by moclobemide: effects on monoamine metabolism and secretion of anterior pituitary hormones and cortisol in healthy volunteers.

1. Single oral doses (100, 200 and 300 mg) of moclobemide, a reversible inhibitor of monoamine oxidase (MAO) with predominant effects on the A-type of the enzyme, were administered to eight young, healthy male volunteers in a double-blind, random-order, placebo-controlled study. The investigation was thereafter continued in an open fashion by administering a single 10 mg dose of the MAO-B inhibitor deprenyl to the same subjects. 2. Deamination of catecholamines was powerfully and dose-dependently inhibited by moclobemide, as evidenced by up to 40% decreases in the urinary excretion of deaminated catecholamine metabolites, corresponding increases in the excretion of non-deaminated, methylated metabolites, and up to 79% average decreases in the plasma concentration of 3,4-dihydroxyphenylglycol (DHPG), a deaminated metabolite of noradrenaline (NA), and up to 75% average decreases in the plasma concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC), a deaminated metabolite of dopamine. The urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) was only slightly reduced. In contrast, deprenyl, in a dose which almost totally inhibited MAO-B activity in blood platelets, did not appreciably affect the plasma concentrations of DHPG or DOPAC. 3. Due to the rapid, reversible, dose-dependent and MAO-A specific effect of moclobemide on plasma concentrations of DHPG, it is suggested that DHPG in plasma may be a useful indicator of the magnitude and duration of MAO-A inhibition in man. 4. Sympatho-adrenal function at rest was not significantly altered by moclobemide, as judged by unchanged plasma catecholamine concentrations and stable blood pressure and heart rate recordings. 5. Monoamine oxidase type B activity in blood platelets was slightly (less than 30%) and transiently inhibited after moclobemide. 6. The secretion of prolactin was dose-dependently stimulated by moclobemide, whereas the plasma concentrations of growth hormone (hGH) and cortisol remained unchanged.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Effects of oral clonidine premedication on concentrations of cortisol and monoamine neurotransmitters and their metabolites in cerebrospinal fluid and plasma.

Forty-two healthy male patients (aged 19-40 years), undergoing orthopaedic surgery under spinal anaesthesia (3 ml isobaric 0.5% bupivacaine), were given clonidine 4.5 micrograms kg-1 orally either 2 (Group I, n = 10) or 4 (Group II, n = 10) hours before the operation, diazepam 0.15 mg kg-1 orally (Group III, n = 10) or a placebo tablet (Group IV, n = 12) 2 h before the operation. Plasma concentrations of cortisol, noradrenaline (NA), adrenaline (A), 3,4-dihydroxyphenylglycol (DHPG) and dihydroxyphenylacetic acid (DOPAC) were assayed from venous blood samples just before premedication and just before the spinal block. Cerebrospinal fluid (CSF) concentrations of cortisol, tryptophan, 5-hydroxyindoleacetic acid and catecholamine metabolites were assayed from a sample taken before the spinal block. The plasma NA concentrations of the patients in the groups receiving clonidine decreased clearly compared with the other groups (P less than 0.05). The NA metabolite DHPG was also lower in Groups I and II than in Group III (P less than 0.05) after premedication. Plasma A concentrations were lower in Groups I and III than in Group IV (P less than 0.05). The CSF concentrations of the different substances were similar in all groups. In Group I the sensory blockade lasted significantly longer than in Group III (P less than 0.05) and the mean duration of motor blockade was longer in Group I than in Groups III and IV (P less than 0.05). Two patients in both clonidine groups developed bradycardia (heart rate less than 45 min-1) requiring atropine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Hormonal, haemodynamic, and subjective effects of intravenously infused indomethacin: no change in the physiological response to hypertonic saline challenge.

This double-blind, placebo-controlled human study was performed to determine the endocrine responses to intravenously administered indomethacin at two dose rates (0.36 or 0.72 mg/kg bolus followed by 0.071 or 0.143 mg/kg/hr for 150 min.). A 5% hypertonic saline infusion was used for further assess the hormonal systems regulating body fluid and electrolyte balance. Plasma renin activity (PRA) and concentrations of aldosterone and vasopressin (AVP) were unaffected by indomethacin. Hypertonic saline caused a 5% increase in plasma sodium and a 4.2% increase in serum osmolality, with a concomitant two-fold rise in plasma AVP levels and significant declines in PRA and aldosterone. Indomethacin had no effects on these responses, and did not affect plasma catecholamine concentrations, but the hypertonic saline infusion doubled the noradrenaline levels in plasma. Atrial natriuretic peptide (ANP)-like immunoreactivity in plasma was not affected by indomethacin nor by hypertonic saline. The higher dose rate of indomethacin resulted in significant stimulation of growth hormone release, but plasma prolactin levels were not influenced. Thus acute intravenous administration of indomethacin proved to be devoid of significant effects on the multihormonal system regulating fluid and electrolyte balance.

Adult↗
PubMed1989

An introduction to the pharmacology of alpha 2-adrenoceptors in the central nervous system.

alpha 2-Adrenoceptors mediate a variety of physiological functions in the central nervous system and in peripheral tissues; thus, the use of pharmacological agents either activating or blocking these receptors results in a mixture of responses from several organs and tissues. This may be utilized therapeutically in some situations. In anaesthesiology, alpha 2-adrenergic agonists are already widely used as veterinary sedative-analgesics, and it is now clear that they are also capable of potentiating the effects and reducing the required dosage of other drugs used in anaesthesia (barbiturates, volatile anaesthetics, narcotic analgesics). In addition, they attenuate sympatho-adrenal responses to noxious stimuli encountered during anaesthesia and surgery, providing improved hemodynamic, metabolic and hormonal stability. Recent results from molecular biology, biochemistry and pharmacology point to the existence of distinct alpha 2-adrenoceptor subtypes. The identification of such subpopulations of alpha 2-adrenoceptors may provide new opportunities for the development of subtype-selective pharmacological agents with more specific therapeutic actions.

Adrenergic alpha-Agonists↗
PubMed1989

Pharmacological effects of medetomidine in humans.

Single i.v. doses of medetomidine have been administered to healthy male volunteers in three clinical phase I studies. After an initial open dose-finding study, double-blind, placebocontrolled designs were used. The highest dose tested was 120 micrograms. Medetomidine was well tolerated. It caused dose-dependent decreases of blood pressure (max 22/14 mmHg), heart rate (max 14/min) and cardiac output (max 21%) without subjective sensations of hemodynamic changes or other unexpected side-effects. However, a clear dose-dependent sedative effect, both subjective and objective, and a decrease in salivation was seen after single i.v. doses. Medetomidine had a powerful and dose-dependent effect in reducing noradrenaline (by a maximum of 75%) and increasing human growth hormone levels in plasma. All the observed pharmacological effects are well compatible with an alpha 2-agonistic action of the drug and resemble those seen after i.v. administration of clonidine. However, medetomidine appeared to be more potent and short-acting than clonidine.

Adrenergic alpha-Agonists↗
PubMed1988

Behavioural and neurochemical effects of medetomidine, a novel veterinary sedative.

The effects of the novel veterinary sedative, medetomidine, were studied in rats. In addition to a dose-dependent sedation, which at high doses (greater than 100 micrograms/kg) included loss of the righting reflex and hypothermia, there was a concurrent decrease in the turnover rate of biogenic amines in the brain. Noradrenaline turnover was dose dependently decreased as judged by (i) the decrease in the brain concentration of its metabolite, MHPG-SO4, (ii) a decrease in the ability of alpha-methyl-p-tyrosine methyl ester to deplete brain noradrenaline stores and (iii) a dose-dependent decrease in the level of unconjugated MHPG in the CSF of freely moving rats. Brain dopamine turnover was also inhibited at higher doses as judged by the alpha-methyl-p-tyrosine method and by a decrease in the concentration of HVA in the rat brain 4 h after medetomidine. Serotonin turnover as estimated by the ratio of biogenic amine to its metabolite was also significantly depressed. These changes in brain biogenic amine turnover were inhibited by prior or simultaneous administration of alpha 2-adrenoceptor antagonists, either yohimbine or the more specific, novel alpha 2-antagonist, atipamezole.

Adrenergic alpha-Agonists↗
PubMed1988

Behavioural and neurochemical effects of antipamezole, a novel alpha 2-adrenoceptor antagonist.

The effects of antipamezole (MPV-1248), a novel selective and specific alpha 2-adrenoceptor antagonist, were studied on monoamine metabolism in rat brain and CSF. In addition, the ability of the drug to antagonize the behavioural and neurochemical effects of two alpha 2-adrenoceptor agonists, detomidine and medetomidine, was assessed. Atipamezole, 0.03-3.0 mg/kg, had no gross behavioral effects on the rats. Above 3 mg/kg, the rats showed increased vocalization and some hostility, rapid breathing and piloerection. The drug caused dose-dependent, rapid and relatively long-lasting increase in the central turnover of noradrenaline (NA) as reflected by increases in the levels of the major metabolites of NA in brain and CSF and an increase in the depleting effect of alpha-methyl-para-tyrosine on brain NA levels. An increase in the turnover of serotonin (5-HT) in brain was indicated by a decrease in the concentration of 5-HT and a corresponding increase in the level of its metabolite, 5-hydroxyindoleacetic acid. Atipamezole was able to antagonize the sedative, hypothermic and neurochemical effects of two potent alpha 2-agonists, detomidine and medetomidine. These results give support for the characterization of atipamezole as a potent antagonist at central alpha 2-adrenoceptors with a rapid onset of action.

Adrenergic alpha-Antagonists↗
PubMed1988

Local dental anaesthesia with lidocaine and adrenaline. Effects on plasma catecholamines, heart rate and blood pressure.

5 volunteers took part in this double-blind, cross-over study to evaluate the role of adrenaline 1:80,000 in lidocaine used in dental local anaesthesia on haemodynamics and the concentrations of catecholamines and their metabolites in plasma. The exogenous adrenaline statistically significantly elevated the heart rate (from 66 +/- 7 to 79 +/- 9 bpm), but did not affect systolic or diastolic blood pressure. Plasma adrenaline concentrations were increased more than 10-fold (from 0.02 +/- 0.02 to 1.0 +/- 0.3 nmol/l). We conclude that the adrenaline present in the local anaesthetic is a major source of adrenergic activation during minor oral surgery.

Adult↗
PubMed1988

Dissociation of norepinephrine turnover from alpha-2 responses after clorgiline.

Responses to intravenous clonidine, a possible central noradrenergic probe, were examined in patients with depression before and after treatment with clorgiline, a selective monoamine oxidase type A inhibitor. Pulse rate, mean arterial blood pressure, plasma norepinephrine, 3-methoxy-4-hydroxyphenylglycol, and growth hormone were measured. Clorgiline treatment (2.5 to 10 mg/day) produced a variable reduction in the hypotensive response to clonidine but did not influence heart rate or plasma norepinephrine responses. Clorgiline markedly reduced the urinary output of norepinephrine and metabolites, indicating a reduced turnover of norepinephrine. None of the measured parameters corresponded with clinical effect. These data suggest that any clorgiline-induced alterations in alpha 2-receptor function as measured by responses to clonidine are modest and highly variable. Furthermore, since the variable and inconsistent changes in alpha 2-receptor function are dissociated from the massive changes in norepinephrine metabolism, regulation of presynaptic alpha 2-receptors appears unlikely to mediate the effects of clorgiline in patients with depression.

Bipolar Disorder↗