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Biomedical subjects

H Scheinin

Publications and source records attributed to H Scheinin.

At least 55 records · Page 3Linked to original sources
PubMed1998

Biological day-to-day variation and daytime changes of testosterone, follitropin, lutropin and oestradiol-17beta in healthy men.

Information on biological day-to-day variation is needed for detecting within-subject changes over time. In this study the daytime changes and the biological day-to-day variation of serum testosterone, follitropin, lutropin and oestradiol-17beta concentrations were investigated in 31 healthy males. To analyse daytime changes, blood specimens were taken at 0800 h, 1200 h, 1600 h and 2000 h during one day (n=31) and two days (n=8). The day-to-day variation was analysed from blood specimens collected at 0800 h on days 1 and 2 (n=31) and additionally on days 3, 4, 6 and 9 (n=8). The evaluation of the day-to-day variation was based on calculations of the within-subject (CVA+I) and between-subject (CV(G)) coefficients of variation. When the within-subject day-to-day variances were not too heterogeneous, they were used for the calculation of 95 % reference change limits. Serum testosterone and oestradiol-17beta concentrations showed a significant daytime variation; testosterone had higher serum concentrations at 0800 and 1200 h. A peak in the serum concentration of oestradiol-17beta occurred at 1200 h with a decrease towards the evening. There were no clear daytime changes in the serum concentrations of follitropin or lutropin. For different analytes the reference change limits were: serum testosterone +/- 32.0 %, serum follitropin +/- 24.1 % and serum oestradiol-17beta +/- 38.3 %. The reference change limit was not calculated for serum lutropin, as a high degree of heterogeneity and individuality was found. The interpretation of the results of hormone measurements requires recognition of the biological daytime and day-to-day changes of hormones. The reference change limits determine what changes are significant when monitoring the patient.

Adult↗
PubMed1998

Integrated pharmacokinetics and pharmacodynamics of the novel calcium sensitizer levosimendan as assessed by systolic time intervals.

BACKGROUND: Levosimendan is a new calcium sensitizer, acting calcium-dependently on cardiac troponin C. In the present study pharmacokinetic-pharmacodynamic interrelations of levosimendan were assessed. SUBJECTS AND METHODS: Ten healthy subjects (22-27 years) were given single doses of 2 mg of levosimendan in 4 different formulations: intravenous (i.v.), conventional tablet (CT), conventional capsule (CC), and slow-release tablet (SR) on different days. Systolic time intervals and impedance cardiography were recorded up to 4 hours post drug. Plasma concentrations of levosimendan and its metabolite OR-1855 were analyzed using HPLC. Hysteresis loops were constructed by connecting the effect-concentration points in time order. In addition, pharmacokinetic-pharmacodynamic modelling was performed with the i.v. data. RESULTS: The i.v. administration, giving a maximal levosimendan concentration of 180 ng x ml(-1), increased heart rate by 8 beats min(-1) and cardiac output by 18%. It shortened heart rate corrected electromechanical systole QS2i by 23 ms, indicating a fairly strong positive inotropic effect. The conventional oral formulations (giving maximal drug concentrations of about 70-80 ng x ml(-1)) increased heart rate by 4-5 beats min(-1) and cardiac output by 5-8%, while QS2i shortened by 9-13 ms. The SR formulation resulted in low drug concentrations and generally weaker effects than the other formulations. The bioavailability of CT and CC was 83 and 87%, while that of SR was only 31%. QS2i showed counter-clockwise hysteresis after all formulations (p < 0.01). The mean equilibration half-time (ln(2)/k(e0)) after i.v. administration was 9.6 min. Only after SR, OR-1855 was detected in appreciable amounts in plasma, the highest value being 2.2 ng x ml(-1) which occurred 24 hours after drug intake. CONCLUSION: In conclusion, the pharmacokinetic-dynamic behavior of the inotropy index QS2i indicates an equilibration delay of levosimendan, which most probably reflects the time the drug requires to distribute from plasma to its cardiac site of action. The deviant kinetic-dynamic profile of the oral slow-release formulation suggests a different absorption pattern of levosimendan from this formulation.

Administration, Oral↗
PubMed1997

A medication database--a tool for detecting drug interactions in hospital.

OBJECTIVE: Drug interactions may lead to life-threatening injuries. More often, however, they lead to slow recovery, induce slight symptoms or result only in potential injury. Therefore, clinicians are not always aware of using potentially interacting drug combinations. An on-line alarming system of potential drug interactions was developed in Turku University Central Hospital. In the present study, we utilised the system to find out the incidence and nature of potential drug interactions occurring in a representative hospital patient population. METHODS: Computerised anatomical therapeutic chemical (ATC)-coded patient medication data of 2547 patients, treated in two internal medicine wards, were combined with an ATC-coded rule base of drug interactions. All potential drug interactions in the study population were searched for. RESULTS: A total of 326 potentially serious drug interactions were detected in the study population. The number of patients in this group was 173, i.e. 6.8% of all patients had one or several drug combinations which might have led to serious clinical consequences. Concomitant use of calcium and fluoroquinolones (decreased absorption) was the most common mistake (66 prescriptions). CONCLUSIONS: Potentially inappropriate drug combinations seem to occur frequently. Structured and coded medication data can be utilised efficiently to detect potential drug interactions in hospital. Computerised online monitoring and automatic alarming of potentially hazardous drug combinations might help clinicians to prescribe more safely, but further development of the system is needed to avoid unnecessary alarms.

Clinical Pharmacy Information Systems↗
PubMed1996

Single-dose i.v. granisetron in the prevention of postoperative nausea and vomiting.

In this randomized, double-blind, parallel group, placebo-controlled, dose-ranging study, we have compared three doses (0.1 mg, 1.0 mg and 3.0 mg) of the 5-HT3 receptor antagonist, granisetron (Kytril), as prophylactic therapy for the prevention of postoperative nausea and vomiting. The aims were to determine the optimal dose of granisetron and to evaluate its safety profile. We studied 527 adult patients, undergoing elective open abdominal surgery or vaginal hysterectomy during general anaesthesia. Antiemetic prophylaxis with a single dose of granisetron 1.0 mg or 3.0 mg resulted in a significant reduction (P < 0.001 compared with placebo) in the numbers of patients experiencing postoperative vomiting, or nausea, or who achieved total control during the postoperative periods 0-6 h and 0-24 h. The two higher doses of granisetron (1.0 mg and 3.0 mg) provided effective prophylaxis against vomiting, with 78% and 77% of patients, respectively, being free from vomiting in the first 6 h after surgery, and 63% and 62% in the first 24 h. This compares with 50% and 34% at 0-6 h and 0-24 h, respectively, in the placebo group. Granisetron was well tolerated and the optimum dose was 1.0 mg.

Adult↗
PubMed1996

Biochemical and clinical assessment of histamine blockade.

The effects of antihistamines on biochemical stress indicators and on psychomotor and physiological functions were studied in 60 healthy patients receiving in a randomized, double-blind study either 25 mg promethazine, 150 mg ranitidine, both drugs or placebo (n = 15 in each group). Different aspects of the premedications were evaluated by determining various hormone, neurotransmitter and neurotransmitter metabolite levels in blood and cerebrospinal fluid, and subjectively using questionnaires concerning the quality of the preoperative night's sleep and visual analogue scales, and objectively by measuring changes in blood pressure and heart rate, impairment of vigilance with the Maddox wing apparatus and the critical flicker fusion threshold test. The relationships between the subjective assessments and the biochemical stress indicators were also investigated. There were no differences between the study groups in the quality of the preoperative night's sleep, estimated fear, apprehension or dizziness, or in the various physiological stress indicators. Only few statistically significant correlations were found between the subjective and biochemical assessments. It is concluded that histamine receptor antagonists used in clinical doses do not interfere with the biochemical, clinical preoperative, and physiological responses.

Adult↗
PubMed1995

Buccal delivery of an alpha 2-adrenergic receptor antagonist, atipamezole, in humans.

OBJECTIVE: To evaluate the pharmacokinetics, systemic effects and clinical applicability of buccally administered atipamezole in healthy volunteers. METHODS: The study was carried out in two parts. In the first part, spray preparations of atipamezole hydrochloride in water/alcohol (50/50) solution were applied on buccal mucosa of six volunteers. Single doses of 5, 10, 20, and 40 mg atipamezole hydrochloride were administered in ascending order during separate sessions. In the second part, nine subjects received single 20 mg doses as buccal spray, intravenous infusion, or oral solution in randomized order. RESULTS: Values for area under the concentration-time curve for atipamezole (mean +/- SD) ranged from 26 +/- 4 ng x hr/ml after 5 mg to 112 +/- 21 ng x hr/ml after 40 mg and peak concentrations ranged from 11 +/- 3 ng/ml after 5 mg to 38 +/- 9 ng/ml after 40 mg. Individual peak concentrations were mainly measured at 30 and 60 minutes after administration. Mean elimination half-lives were approximately 1 1/2 hours after every treatment. In part two, a mean bioavailability of 33% was calculated for buccal administration (compared with intravenous), whereas systemic availability after an oral dose was < 2%. After intravenous administration the mean total clearance, apparent volume of distribution, and elimination half-life were 1.2 L/hr/kg, 2.9 L/kg, and 1.8 hours, respectively. The intravenous administration of 20 mg atipamezole hydrochloride produced a fivefold elevation in mean plasma norepinephrine concentration, a slight and short-lasting elevation in blood pressure and, in most subjects, increased tension, alertness and restlessness, and sweating. After buccal administration, some subjects reported short-lasting restlessness or tension after the 20 and 40 mg doses. No significant changes in heart rate, blood pressure, or plasma catecholamines were observed. No effects were observed after swallowing of 20 mg atipamezole hydrochloride. The spray caused local reactions at buccal mucosa. Superficial white spots or areas were observed for several hours; these disappeared gradually. Subjects also reported transient numbness at the application site. CONCLUSION: Atipamezole hydrochloride is well absorbed systemically through oral mucosa. The oral bio-availability of atipamezole is negligible, probably because of extensive first-pass metabolism.

Administration, Buccal↗
PubMed1995

Dexmedetomidine premedication attenuates ketamine-induced cardiostimulatory effects and postanesthetic delirium.

BACKGROUND: Dexmedetomidine is a new potent and highly selective alpha 2-adrenoceptor agonist with sedative-hypnotic and anesthetic sparing properties. Because of its sympathoinhibitory activity, it may prove useful in balancing the cardiostimulatory effects and attenuating the adverse central nervous system effects of ketamine. METHODS: A double-blind, randomized and comparative parallel-group study design was employed in 40 volunteers with ASA physical status 1 who were scheduled for elective superficial surgery under ketamine anesthesia. Dexmedetomidine (2.5 micrograms/kg, n = 20) or midazolam (0.07 mg/kg, n = 20) was administered intramuscularly 45 min before induction of anesthesia. Anesthesia was induced with 2 mg/kg ketamine intravenously, and muscle relaxation was achieved with vecuronium. After tracheal intubation, anesthesia was maintained with nitrous oxide/oxygen (2:1) and additional 1 mg/kg intravenous ketamine boluses according to clinical and cardiovascular criteria. Hypotension and bradycardia were treated by increasing the intravenous infusion rate of crystalloids and intravenous atropine, respectively. Sedative and anxiolytic properties, intra- and postoperative drug requirements, psychomotor and cognitive impairments, and cardiovascular effects were compared between the two groups. RESULTS: Dexmedetomidine and midazolam proved to have equal sedative and anxiolytic effects after intramuscular administration, but dexmedetomidine induced significantly less preoperative psychomotor impairment and less anterograde amnesia than did midazolam. Compared to midazolam, dexmedetomidine decreased the need for intraoperative ketamine and was more effective in reducing ketamine-induced adverse central nervous system effects. Dexmedetomidine also was superior to midazolam in attenuating the hemodynamic responses to intubation and the cardiostimulatory effects of ketamine in general, but it increased the incidence of intra- and postoperative bradycardia. CONCLUSIONS: These results suggest that premedication with 2.5 micrograms/kg dexmedetomidine is effective in attenuating the cardiostimulatory and postanesthetic delirium effects of ketamine. However, because of its propensity to cause bradycardia, routine use of an anticholinergic drug should be considered.

Adolescent↗
PubMed1994

Aspoxicillin versus piperacillin in severe abdominal infections--a comparative phase III study.

We compared aspoxicillin, a new broad-spectrum penicillin derivative, with piperacillin in severe abdominal infection. Aspoxicillin 4 g administered tds (n = 52) or piperacillin 4 g qds (n = 53) usually as monotherapy were randomly given to patients suffering from perforated appendicitis, acute cholecystitis, ulcer or colon perforation, or intra-abdominal abscess. Blood, tissue and exudate cultures were obtained when applicable for pathogen identification and susceptibility testing. The efficacy rates were similar in the two study groups. Of the 50 evaluable aspoxicillin patients 45 (90%) were considered as treatment responders compared with 48 patients out of 53 (91%) in the piperacillin group (NS). The 95% confidence interval for the efficacy difference was -12% to +11% thus showing no difference between the two drugs. Both drugs were generally well tolerated and no serious drug-related adverse events were noted. However, five patients died because of their illness and one patient had a fatal myocardial infarction. In conclusion, aspoxicillin 4 g tds was shown to be equal to piperacillin 4 g qds in severe abdominal infections.

Abdominal Abscess↗
PubMed1994

Dexmedetomidine as intramuscular premedication for day-case cataract surgery. A comparative study of dexmedetomidine, midazolam and placebo.

The effects of dexmedetomidine 1.0 microgram.kg-1, midazolam 20 micrograms.kg-1 and saline placebo were assessed in a double-blind, randomised study in 90 patients undergoing day-case cataract surgery under regional anaesthesia. The trial drug was injected into the deltoid muscle 45 min before the peri-ocular block. Dexmedetomidine 1.0 microgram.kg-1 decreased intra-ocular pressure before, during and after surgery. The maximum reduction in mean (SD) intra-ocular pressure occurred in the dexmedetomine group just before discharge from hospital (17.7 (2.8) mmHg to 11.5 (2.9) mmHg) (p < 0.001 compared with midazolam and placebo). In contrast, midazolam did not differ from saline placebo. Dexmedetomidine and midazolam produced a similar sedative effect of short duration. Dexmedetomidine induced a moderate decrease in blood pressure (p < 0.001 compared with placebo) and a slight but statistically significant decrease in heart rate throughout the study period (p < 0.001 compared with placebo). Dexmedetomidine 1.0 microgram.kg-1 intramuscularly, effectively reduced intra-ocular pressure and produced short-acting sedation with marginal cardiovascular effects; it may be a useful premedicant drug for elderly patients undergoing day-case cataract surgery under regional anaesthesia.

Adrenergic alpha-Agonists↗
PubMed1994

Intramuscular dexmedetomidine premedication--an alternative to midazolam-fentanyl-combination in elective hysterectomy?

Sedation, anxiolysis, intubation responses and fentanyl anaesthetic requirements were investigated in a double-blind, randomized study in twenty ASA I-II elective hysterectomy patients. Ten patients received dexmedetomidine 2.5 micrograms kg-1 i.m. 60 min before induction and saline placebo i.v. 2 min prior to induction (= DP group). Ten patients received midazolam 0.08 mg kg-1 i.m. 60 min and fentanyl 1.5 micrograms kg-1 i.v. (= MF group) 2 min before induction of anaesthesia with thiopentone 4 mg kg-1. Anaesthesia was maintained with 70% nitrous oxide in oxygen and with fentanyl 2 micrograms kg-1 i.v. increments according to predetermined criteria. Both premedications induced sedation (P < 0.01 in both groups) and anxiolysis (P < 0.01 in DP vs P < 0.05 in MF group) without any differences between the groups. Haemodynamic changes following tracheal intubation did not significantly differ between the groups. Intraoperatively systolic and diastolic arterial pressure were 15% and 13% lower in DP group (P < 0.01 and P < 0.05 for drug effect), the mean heart rate was approximately 9 beats min-1 lower in DP group (n.s.). Fentanyl was required more often in MF group: median 3.5 (QD 1.5) vs. 2.5 (QD 0.5) times in DP group (P < 0.05), the total amount being 57% smaller in DP group: 0.03 (QD 0.01) vs. 0.07 (QD 0.02) micrograms kg-1 min-1 (P < 0.05). Postoperative course and analgesic requirements were similar in both groups. Dexmedetomidine premedication may offer an alternative to current anaesthesia practice in elective hysterectomy.

Adrenergic alpha-Agonists↗
PubMed1993

Intramuscular dexmedetomidine as premedication for general anesthesia. A comparative multicenter study.

BACKGROUND: Dexmedetomidine is a new potent and selective alpha 2-agonist that might prove useful as a preanesthetic agent. METHODS: A randomized, double-blind study design was used in 192 ASA physical status 1 and 2 patients scheduled for elective abdominal hysterectomy, cholecystectomy, or intraocular surgery under general anesthesia. Intramuscular injection of 2.5 micrograms/kg dexmedetomidine administered 60 min before and intravenous saline placebo 2 min before induction of anesthesia (DEXPLA group, n = 64) was compared with a combination of 0.08 mg/kg intramuscular midazolam 60 min and 1.5 micrograms/kg intravenous fentanyl 2 min before induction (MIDFENT group, n = 64), or a combination of intramuscular dexmedetomidine and intravenous fentanyl (DEXFENT group, n = 64). After thiopental induction, anesthesia was maintained with 70% N2O/O2, and fentanyl was administered according to clinical and cardiovascular criteria. Patients undergoing cholecystectomy received additional enflurane. RESULTS: Dexmedetomidine and midazolam induced comparable preoperative sedation and anxiolysis. The DEXFENT combination blunted the increases in blood pressure and heart rate induced by tracheal intubation more efficiently when compared with the DEXPLA and MIDFENT groups, in which approximately 25 mmHg and 15 beats/min greater increases were observed. The intraoperative fentanyl requirements were greater in MIDFENT patients when compared with both dexmedetomidine groups, in which 56% (DEXFENT group) and 31% (DEXPLA group) less fentanyl, respectively, was needed. Intraoperatively, fluids or vasopressors for hypotension and glycopyrrolate for bradycardia were administered more often to patients receiving dexmedetomidine than to those who did not. Postoperatively, there were no differences in oxygen saturation, analgesic, or antiemetic requirements, but dexmedetomidine-induced blood pressure and heart rate reductions were still evident at the end of the 3-h follow-up period. Bradycardia as an adverse event was reported more frequently in dexmedetomidine patients (20% in the DEXPLA and 33% in the DEXFENT groups) than in MIDFENT patients (8%). CONCLUSIONS: The results suggest that pretreatment with a single intramuscular injection of 2.5 micrograms/kg dexmedetomidine is efficacious, but significantly increases the incidence of intraoperative hypotension and bradycardia in ASA physical status 1 or 2 patients.

Adult↗
PubMed1993

Dexmedetomidine as intramuscular premedication in outpatient cataract surgery. A placebo-controlled dose-ranging study.

Alpha 2 agonists have been shown to decrease intra-ocular pressure in ophthalmic surgery. We studied the effects of dexmedetomidine, a new alpha 2 agonist, on intra-ocular pressure, haemodynamic parameters, sedation, anxiolysis and dryness of mouth in 35 (ASA physical status 1-3) patients undergoing day-case cataract surgery under peri-ocular anaesthesia. Five different doses of dexmedetomidine (0.25, 0.5, 0.75, 1.0 and 1.5 micrograms.kg-1) were used in this double-blind, randomised and placebo-controlled study. The trial drug was administered into the deltoid muscle 60 min before surgery. The 1.0 micrograms.kg-1 dose of dexmedetomidine produced a 32% reduction of intra-ocular pressure (p = 0.002). This dose induced moderate sedation, but was not associated with significant haemodynamic changes. A significant decrease in heart rate and systolic blood pressure was seen only with the highest dose of dexmedetomidine. Our results suggest that dexmedetomidine 1.0 micrograms.kg-1 produces sedation and a reduction of intra-ocular pressure with minimal haemodynamic side effects when given intramuscularly as premedication before cataract surgery under regional anaesthesia.

Adrenergic alpha-Agonists↗
PubMed1993

Reduced turnover of dopamine and 5-hydroxytryptamine in discrete dopaminergic, noradrenergic and serotonergic rat brain areas after acutely administered medetomidine, a selective alpha 2-adrenoceptor agonist.

Monoamine metabolism and turnover were investigated in discrete dopaminergic, noradrenergic and serotonergic brain areas in the rat after acute administration of the selective alpha 2-adrenoceptor agonist, medetomidine. Medetomidine (3, 30 and 100 micrograms/kg subcutaneously) was given 90 min. before decapitation and discrete brain nuclei were punched from frozen brain slices for the analysis of concentrations of noradrenaline (NA), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA). In a separate experiment, the accumulation of 3,4-dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP) was measured after inhibition of L-aromatic amino acid decarboxylase by NSD 1015: medetomidine (3, 10 and 100 micrograms/kg subcutaneously) was given 60 min. before NSD 1015 (100 mg/kg intraperitoneally), and the rates of DOPA and 5-HTP accumulation were determined over 30 min. Finally, the antagonistic effect of idazoxan (1 mg/kg subcutaneously), a selective alpha 2-adrenoceptor blocking agent, on the medetomidine-induced changes in monoamine metabolism was investigated. Medetomidine markedly decreased the metabolism and turnover of DA in the nucleus caudatus, but not in the nucleus accumbens or substantia nigra. In all dopaminergic areas, the turnover of 5-HT was markedly inhibited by medetomidine. These effects were significantly counteracted by idazoxan pretreatment demonstrating the alpha 2-receptor mediated action of medetomidine. The turnover of 5-HT was also reduced by medetomidine in the nucleus raphe dorsalis, the A1-C1 area, locus coeruleus, nucleus tractus solitarius and the A5 area. The accumulation of DOPA was markedly inhibited in the A1-C1 area, nucleus tractus solitarius and nucleus raphe dorsalis, but not in locus coeruleus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1992

Pharmacodynamics and pharmacokinetics of intramuscular dexmedetomidine.

The pharmacodynamics and pharmacokinetics of intramuscular dexmedetomidine--a novel alpha 2-adrenergic receptor agonist under development for preanesthetic use--were studied in healthy male volunteers. Single intramuscular doses of dexmedetomidine (0.5, 1.0, and 1.5 microgram/kg) and placebo were administered to six subjects in a single-blind, multiple crossover study. Dexmedetomidine induced dose-related impairment of vigilance assessed both objectively and subjectively. The drug also caused moderate decreases in blood pressure and heart rate. Plasma norepinephrine was dose-dependently (maximum 89%) decreased. The intramuscular doses resulted in linearly dose-related plasma concentrations of dexmedetomidine. Pharmacokinetic calculations revealed a time to maximum concentration from 1.6 to 1.7 hours, an elimination half-life of 1.6 to 2.4 hours, an apparent total plasma clearance of 0.7 to 0.9 L/hr/kg, and apparent volume of distribution of 2.1 to 2.6 L/kg. The sedative effect of dexmedetomidine dissipated during the 6-hour observation time, but all other effects were still evident 6 hours after administration of the higher doses, paralleling the plasma concentration curves. The relationship of plasma concentrations of dexmedetomidine to pharmacodynamic variables was consistent with a linear pharmacodynamic model. The pharmacodynamic-pharmacokinetic profile of intramuscular dexmedetomidine may be suited to the proposed preanesthetic clinical use of this alpha 2-agonist.

Adrenergic alpha-Agonists↗
PubMed1992

Dexmedetomidine attenuates sympathoadrenal responses to tracheal intubation and reduces the need for thiopentone and peroperative fentanyl.

The effects of the new, highly selective alpha 2-adrenergic agonist, dexmedetomidine, were studied in a randomized, placebo-controlled, double-blind trial in 24 ASA I patients. Dexmedetomidine 0.6 micrograms kg-1 or saline was given i.v. 10 min before induction of anaesthesia. The required dose of thiopentone was significantly (P less than 0.001) smaller in the dexmedetomidine group (mean 4.4 (sd 0.9) mg kg-1) than in the control group (6.9 (1.6) mg kg-1), and the drug attenuated the cardiovascular responses to laryngoscopy and tracheal intubation. The concentration of noradrenaline in mixed venous plasma was smaller in the dexmedetomidine group during all phases of induction (P less than 0.01). During surgery, fentanyl was required in a dose of 0.5 (0.6) mg kg-1 and 2.8 (2.6) mg kg-1 in the dexmedetomidine and control groups, respectively (P less than 0.001). During 2 h postoperative follow-up, oxycodone 0.06 (0.06) mg kg-1 and 0.16 (0.1) mg kg-1 (P less than 0.05) was given to the two groups respectively.

Adrenergic alpha-Agonists↗