Biomedical subjects

T Kaila

Publications and source records attributed to T Kaila.

At least 19 recordsLinked to original sources

PubMed2005

Propranolol increases the complexity of heart rate fluctuations--a mode of antiarrhythmic action?

OBJECTIVE: To study the beta-blocking effect of propranolol on heart rate and arterial blood pressure fluctuations in healthy subjects using linear methods and a set of nonlinear models. METHODS: In a randomized, double-blind, placebo-controlled study, healthy young adults received a 40 mg oral dose of propranolol (n = 12) or placebo (n = 12). The effects of propranolol and placebo were assessed using time series of the RR interval (RRI) and systolic arterial blood pressure (SAP) obtained from continuous ECG and blood pressure signal recordings. Heart rate and systolic arterial blood pressure fluctuations were analyzed using nonlinear and linear methods of time series statistics. RESULTS: Propranolol significantly increased the complexity of heart rate fluctuations in terms of symbol dynamic (SymDyn) entropy and symbol dynamic percentage of forbidden words. Propranolol augmented cross entropy between RRI and SAP and increased fractal dimension of RRI. beta-blockade also affected linear measures of RRI fluctuations by increasing parasympathetic, respiration-related high-frequency (HF) variability and arterial baroreflex-related low-frequency (LF) variability. Propranolol administration, however, had no effect on the complexity of SAP fluctuations assessed using nonlinear time series statistics. CONCLUSIONS: beta-blockade by propranolol has a differential effect on RRI and SAP fluctuations in healthy subjects. Propranolol increases the complexity of RRI fluctuations. The effect is associated with the cardiac vagotonic drug action of propranolol. SAP fluctuations are almost unchanged. The increased complexity of RRI fluctuations may be a beneficial feature of beta-blockade, since many cardiovascular diseases decrease the complexity of RRI time series by dampening cardiovascular reflex actions.

Administration, Oral↗

PubMed2004

Effects of atipamezole--a selective alpha-adrenoceptor antagonist--on cardiac parasympathetic regulation in human subjects.

1 This double-blind, cross-over, placebo-controlled study on six healthy male volunteers was designed to evaluate the effects of alpha2-adrenoceptor antagonism on cardiac parasympathetic regulation. 2 The subjects received atipamezole intravenously as a three-step infusion, which aimed at steady-state serum concentrations of 10, 30 and 90 ng ml(-1) at 50-min intervals. 3 Drug effects were assessed with repeated recordings of blood pressure and electrocardiogram, in which the high-frequency (0.15-0.40 Hz) R-R interval variation is supposed to reflect cardiac parasympathetic efferent neuronal activity. 4 At the end of the three steps of the infusion, the mean (+/-SD) concentrations of atipamezole were 10.5 (3.9), 26.8 (5.6) and 81.3 (21.1) ng ml(-1). 5 Within this concentration range, atipamezole appeared to reduce slightly the high-frequency R-R interval fluctuations, indicating a minor vagolytic effect in the heart. 6 Atipamezole increased systolic and diastolic arterial pressure, on average by 20 and 14 mmHg (maxima at the second step of the infusion), which evidently reflects an overall sympathetic augmentation.

Adrenergic alpha-2 Receptor Antagonists↗

PubMed2002

Cardiovascular effects of ophthalmic 0.5% timolol aqueous solution and 0.1% timolol hydrogel.

The objective of this randomized, double-masked, cross-over study was to compare the cardiovascular effects of two glaucoma formulations, ophthalmic 0.5% timolol aqueous solution and 0.1% timolol hydrogel. Twenty-four young healthy subjects received for 2 weeks either twice daily 0.5% timolol solution or once daily 0.1% timolol hydrogel. Heart rate (HR), blood pressure, atrio-ventricular conduction (PR interval), corrected QT time (QTc) and heart rate variability (HRV) were measured in supine position and during head-up tilted position. The mean peak concentrations of timolol in plasma were significantly higher after administration of 0.5% aqueous solution than after 0.1% hydrogel. A 0.5% timolol aqueous solution decreased HR on average by 3 bpm in supine position and by 7 bpm in head-up tilted position while no significant effects were observed with 0.1% timolol hydrogel. During tilt test HR was significantly lower after administration of timolol aqueous solution than after timolol hydrogel (mean +/- SD, 77 +/- 11 bpm versus 86 +/- 13 bpm, P < 0.05). Timolol aqueous solution slightly decreased QTc during tilt (5.9 +/- 5.6 ms, P < 0.01). During tilt tests, timolol aqueous solution slightly increased atrio-ventricular conduction (7.2 ms, P = 0.02). No significant differences were found in HRV. These results indicate that in healthy volunteers, ophthalmic 0.5% timolol aqueous solution produces more pronounced cardiac beta-blocking effects than 0.1% timolol hydrogel.

Adult↗

PubMed2001

Spontaneous baroreflex sensitivity as a dynamic measure of cardiac anticholinergic drug effect.

1. In this study, the analysis of spontaneous baroreflex sensitivity (BRS) was applied to the dynamic assessment of cardiac anticholinergic drug effect in healthy male volunteers. 2. The anticholinergic effects of single intravenous (i.v.) injections of atropine (10 microg kg(-1)), glycopyrrolate (5 microg kg(-1)) and scopolamine (5 microg kg(-1)), as well as a 2-h infusion of glycopyrrolate (5 microg kg(-1) h(-1)) were investigated. Baroreflex sensitivity, a validated measure of cardiac parasympathetic reflex regulation, was repeatedly measured from 5-min recordings of electrocardiogram (ECG) and continuous blood pressure by using the sequence technique, a method based on detection of spontaneous fluctuations in blood pressure and heart rate. 3. Single injections of atropine, glycopyrrolate and scopolamine decreased the mean BRS by 71 +/- 32, 68 +/- 23 and 27 +/- 45%, respectively, whereas the slow glycopyrrolate infusion gradually decreased BRS (up to 83 +/- 11% reduction) and increased both systolic (SAP) and diastolic arterial pressures (DAP) (on an average, by 9 mmHg). 4. During the withdrawal of the parasympathetic blockade (indicated by increasing BRS), the proportion of baroreflex sequences in the recordings increased transiently from 10 up to 20-25%, probably reflecting the restoration of the baroreflex integrity and the baroreflex-induced attempt to counteract the blood pressure increase. 5. The sequence method to study BRS seems to be feasible in the assessment of cardiac anticholinergic drug effects, and it also provides good time resolution for the dynamic measurements.

Adult↗

PubMed1999

Systemic bioavailability of ocularly applied 1% atropine eyedrops.

PURPOSE: To investigate the pharmacological basis of systemic effects of atropine eyedrops, we estimated the bioavailability of ophthalmic 1% atropine solution in healthy volunteers. METHODS: In a randomized crossover study we administered 0.3 mg atropine either intravenously or ocularly to six healthy volunteers. The plasma concentrations of the biologically active atropine enantiomer, 1-hyoscyamine, were determined using a muscarinic cholinoceptor binding assay. RESULTS: The mean area under the curve from zero to infinitum (AUC0-infinity) for 1-hyoscyamine was 1.862+/-0.580 microg/L x hr after intravenous, and 1.092+/-0.381 microl/L x hr after ocular administration (mean+/-sd, n=6), respectively. The mean bioavailability was 63.5+/-28.6% (mean+/-SD, n=6; min 19%, max 95%). Large interindividual differences characterized the absorption and elimination phases of 1-hyoscyamine kinetics. The terminal half-life (t1/2beta) of 1-hyoscyamine in plasma was not affected by the route of drug administration. CONCLUSION: The systemic bioavailability of 1-hyoscyamine was considerable and may explain the systemic anticholinergic side effects reported in association with the clinical use of atropine eyedrops.

Absorption↗

PubMed1999

Spectral analysis of heart rate variability as a quantitative measure of parasympatholytic effect--integrated pharmacokinetics and pharmacodynamics of three anticholinergic drugs.

The time course and concentration-effect relationship of parasympatholytic effects of three anticholinergic drugs were investigated using spectral analysis of heart rate (HR) variability. Single intravenous (i.v.) doses of atropine (10 microg/kg), glycopyrrolate (5 microg/kg), scopolamine (5 microg/kg), and placebo were given to eight healthy volunteers in a double-blind, randomized cross-over study. Electrocardiogram (ECG) was recorded at baseline and 2.5, 5, 10, 20, and 30 minutes, and 1, 1.5, 2, 3, 4, 5, and 6 hours after drug administration, while the subjects breathed at a fixed 0.25 Hz frequency. The powers of two frequency bands (low frequency [LF] = 0.07-0.15 Hz and high frequency [HF] = 0.15-0.40 Hz) were calculated using stationary time series of R-R intervals (RRI) free from ectopic beats. To perform pharmacokinetic-pharmacodynamic (PK-PD) modeling, venous plasma drug concentrations were measured. Atropine and glycopyrrolate, and, to a lesser extent, scopolamine induced decreases in HF power and increases in LF/HF ratio of HR variability, indicating parasympatholytic activity and corresponding changes in sympathovagal balance. Maximal average decreases in HF power were 99%, 94%, and 82%, respectively, but in two scopolamine subjects, a parasympathomimetic effect was dominant. Interindividual variability was least for the Hayano index of HF power (square root (RRI HF-power)/RRI*100), and profound and consistent decreases were seen after atropine and glycopyrrolate. Pharmacokinetics were best fitted to a two-compartment open model, and effect compartment link modeling using the Hayano index was performed with the atropine and glycopyrrolate data. The best description of the PK-PD relationship for both drugs was achieved using the sigmoidal Emax model. Mean (+/-SD) EC50, sigmoidicity factor (gamma), and equilibration rate constant (k(e0)) estimates were 1.35 (+/-0.27) ng/mL, 6.07 (+/-1.98) and 11.0 (+/-5.28) l/h for atropine and 1.35 (+/-0.49) ng/mL, 4.34 (+/-1.55) and 2.26 (+/-0.81) l/h for glycopyrrolate. Spectral analysis of HR variability appears to be a powerful tool in monitoring parasympatholytic drug activity. A sigmoidal Emax model with an extremely steep concentration-response relationship was revealed for atropine and glycopyrrolate. The effects of scopolamine were more incongruous.

Adult↗

PubMed1998

Aqueous humour concentration and the intraocular pressure-lowering effect of topical betaxolol before cataract surgery.

OBJECTIVE: The aim was to study the relationship between aqueous humour betaxolol concentration and intraocular pressure (IOP). METHODS: In this double-blind, randomized study, we administered betaxolol (a) or placebo (b) ocularly to 131 patients scheduled for cataract surgery. The patients were randomly divided into ten groups. In groups 1a and 1b, the drug was scheduled to be instilled 1-2 h, in groups 2a and 2b 12 h, in groups 3a and 3b 24 h, and in groups 4a and 4b 48 h before surgery. The pupil was dilated in all eyes prior to surgery. The IOP was measured with Perkins' applanation tonometer before the instillation of the drug and just before the peribulbar block. Twenty microlitres of 0.5% betaxolol or placebo solution was instilled into the eye. IOP was also measured before instillation of the drug and after 1 2 h in undilated eyes of 20 patients, whose contralateral eye was to be operated on, to rule out the effect of pupil dilation on IOP (groups 5a and 5b). Aqueous humour betaxolol concentrations were analysed using a radioreceptor assay. RESULTS: Betaxolol did not decrease IOP significantly in eyes with pupillary dilation. Both betaxolol and placebo decreased IOP significantly in patients without pupillary dilation, the effect of betaxolol being slightly more pronounced. The betaxolol concentration in aqueous humour was 731 ng m-1 in group la, 2.4 h after drug instillation. Measurable concentrations of betaxolol were also detected in aqueous humour in group 4a 47.7 h after drug administration. CONCLUSION: No correlation between aqueous humour concentration of betaxolol and the effect on IOP was found in eyes where the pupil was dilated before surgery. A single betaxolol dose did not decrease IOP significantly in patients undergoing cataract surgery, but the IOP decreasing effect was, however, clearly seen in patients who did not receive mydriatic drugs. The routine use of topical betaxolol prior to cataract surgery to decrease IOP is not recommended.

Adrenergic beta-Antagonists↗

PubMed1998

Valsalva manoeuvre can be used to study baroreflex sensitivity in pregnancy.

OBJECTIVE: The aim of this study was to assess whether baroreflex sensitivity can be measured in a non-invasive manner with the Valsalva manoeuvre in pregnancy. STUDY DESIGN: Baroreflex sensitivity was measured from the reflex response to phenylephrine injection and phase four of the Valsalva manoeuvre in nine pregnant women at 27 (range 24-33) gestational weeks. RESULTS: Both the phenylephrine test and the Valsalva manoeuvre yielded similar estimates of baroreflex sensitivity (9.3 (4.1) ms/mmHg vs. 8.0 (5.2) ms/mmHg, Pearson's correlation coefficient r = 0.81, P < 0.008, linear regression BRSValsalva (ms/mmHg) = 1.03 x BRSPhenylephrine + 1.59). Comparable changes in heart rate and blood pressure were obtained with the phenylephrine test and the Valsalva manoeuvre. CONCLUSION: The physiological challenge caused by the Valsalva manoeuvre can be used to measure baroreflex sensitivity in pregnancy. A possibility to study baroreflex function non-invasively, without pharmacological intervention, benefits future research of blood pressure regulation in pregnancy.

Adult↗

PubMed1998

Pharmacokinetics and clinical effects of intramuscular scopolamine plus morphine. A comparison of two injection sites.

BACKGROUND: Intramuscular scopolamine plus morphine premedication is traditionally used when prominent sedative or antisialogogue effect is needed. Knowledge of the pharmacokinetics of scopolamine is limited due to low plasma concentrations found after therapeutic doses. This investigation compares the pharmacokinetics and the clinical responses of this drug combination injected into two commonly used injection sites. METHODS: Twelve ASA class 1 patients scheduled for minor surgery under spinal anaesthesia received scopolamine 6 micrograms/kg plus morphine 200 micrograms/kg injected in either deltoid (group D, n = 6) or gluteal (group G, n = 6) muscle. RESULTS: The peak plasma concentrations of scopolamine after deltoid or gluteal injection (2.2 vs 1.6 micrograms/l) and the time they were reached (17 vs 19 min) were comparable. The absorption of morphine was similar in both groups (Tmax 16 min), but the peak plasma concentrations were higher after deltoid injection (71 vs 49 micrograms/l). The individual variation in the elimination half-lives of both scopolamine and morphine was smaller after deltoid injection (T1/2 scopolamine 1.9 +/- 0.7 vs 2.1 +/- 1.1 h, morphine 1.3 +/- 0.7 vs 2.3 +/- 1.5 h). Moderate slowing (25%) of heart rate was found in both groups. A heavy sedation and antisialogogue effect (VAS) was found in both groups with faster occurrence of maximal effect in group D (60 vs 120-180 min). CONCLUSION: More predictable pharmacokinetics and clinical effects of intramuscular scopolamine plus morphine premedication can be achieved after an injection into deltoid muscle.

Anesthesia, Spinal↗

PubMed1998

Systemic and ocular absorption and antagonist activity of topically applied cyclopentolate in man.

Ocular and systemic absorption and antagonist activity of topical 1% cyclopentolate were studied in 11 elderly patients undergoing extracapsular cataract extraction, and in 8 healthy female volunteers. The patients received two 35 microl drops of cyclopentolate unilaterally and the healthy volunteers one 30 microl drop bilaterally to the lower conjunctival cul-de-sac of the eye. The drug concentrations were measured with radioreceptor assay and receptor occupancies with radiooccupancy assay using isolated rat brain muscarinic cholinoceptors. In the patient group, cyclopentolate concentrations in aqueous humour were approximately 3000 times higher than those in plasma. Muscarinic cholinoceptors were occupied totally (more than 99.9%) by aqueous humour and 3-18% by plasma taken at 55-125 min. after the drug application. In healthy volunteers peak plasma concentration of cyclopentolate, 2.06+/-0.86 (mean+/-S.D.) nM, occurred at 53 min., maximum receptor occupancy being 5.9+/-2.1%. The maximum pupillary dilatation occured at 30 min. after the drug application. At the same time the near point of vision was extended to more than 50 cm in all subjects. After topical application plasma receptor occupancy was not high enough to cause any significant changes in heart rate and in PQ time. None of the subjects experienced subjectively or objectively adverse effects to be attributed to cyclopentolate.

Absorption↗

PubMed1998

Pharmacokinetics and oral bioavailability of glycopyrrolate in children.

Based on plasma levels determined with a radioreceptor assay and following a single oral (50 micrograms/kg) and intravenous (5 micrograms/kg) administration of glycopyrrolate in six healthy children operated twice during a several weeks period, a negligible and variable oral bioavailability was found (3.3; 1.3-13.3%) (median;range). No significant changes in heart rate after oral or intravenous administration of the drug could be seen. Oral glycopyrrolate appears to have no place in paediatric premedication.

Adjuvants, Anesthesia↗

PubMed1997

The acute effects of inhaled salbutamol on the beat-to-beat variability of heart rate and blood pressure assessed by spectral analysis.

AIMS: We wanted to study the effects of a 600 micrograms inhaled salbutamol dose on the cardiovascular and respiratory autonomic nervous regulation in eight children suffering from bronchial asthma. METHODS: In this randomized, double-blind, placebo-controlled, crossover study we continuously measured electrocardiogram, finger systolic arterial pressure (SAP) and flow-volume spirometry at baseline as well as 20 min and 2 h after the drug inhalation. The R-R interval (the time between successive heart beats) and SAP variabilities were assessed by using spectral analysis. Baroreflex sensitivity was assessed by using cross-spectral analysis. RESULTS: Salbutamol significantly decreased the total and low frequency (LF) variability of R-R intervals as well as the high frequency (HF) variability of R-R intervals and of SAP. Salbutamol significantly increased the LF/HF ratio of R-R intervals and of SAP, minute ventilation, heart rate and forced pulmonary function in comparison with placebo. The weight of the subjects significantly correlated positively with baroreflex sensitivity and negatively with heart rate after the salbutamol inhalation. CONCLUSIONS: We conclude that the acute salbutamol inhalation decreases cardiovagal nervous responsiveness, increases sympathetic dominance in the cardiovascular autonomic balance, and has a tendency to decrease baroreflex sensitivity in addition to improved pulmonary function.

Administration, Inhalation↗

PubMed1996

Muscarinic receptors and insulin concentration in the rat pancreas after chronic alcohol intake and cholinergic stimulation.

The effects of chronic alcohol intake and carbachol stimulation on pancreatic muscarinic receptor binding and insulin concentrations were studied in the rat pancreas. There was a strong correlation between the number of muscarinic receptors and the concentration of insulin in the pancreas. The concentration of insulin decreased in the pancreas after long-term ethanol exposure and increased after carbachol stimulation. These results indicate that the secretion of insulin is mediated via the muscarinic receptor pathway, and that the changes in the number of muscarinic receptors may have a role in insulin deficiency after long-term alcohol consumption.

Animals↗

PubMed1996

beta-blockade, atrial natriuretic peptide and exercise.

Changes in the release of atrial natriuretic peptide (ANP) and vasopressin (VP) may contribute to the final outcome of beta-adrenoceptor blocking therapy. Therefore, we administered 2 hours before a bicycle exercise test (a 30-minute exercise with 100 W work load) in a randomized, double-blind, placebo-controlled crossover study orally 50 mg atenolol, 80 mg propranolol or 10 mg pindolol to 15 healthy volunteers. Hormone release and sympathoadrenal activation were estimated by measuring plasma ANP-, VP-, adrenaline and noradrenaline concentrations. beta-blockade and -antagonism were estimated by measuring the reduction of exercise-induced tachycardia and the extent to which the drugs occupied rabbit lung beta 1- and rat reticulocyte beta 2-adrenoceptors in the circulating plasma. We noticed clear differences in the animal beta 1- and beta 2-receptor occupancy between these agents. The agents and placebo during the exercise augmented plasma ANP level similarly, on average by 34-72%. Pindolol administration enhanced the decline of plasma ANP level after exercise (ANCOVA rep meas, pindolol vs placebo, p < 0.05). Although pindolol increased the mean plasma VP level by 25% (ANCOVA rep meas for the increase, pindolol vs placebo, p < 0.05), drug effects on plasma VP-level were generally negligible. In conclusion, in healthy volunteers beta 1- and beta 2-antagonism by pindolol, atenolol and propranolol do not markedly potentiate plasma ANP- and VP-responses to physical exercise. The responses are, however, slightly influenced presumably by the beta-agonist activity of pindolol.

Adrenergic alpha-Agonists↗

PubMed1995

Plasma kinetics and antagonist activity of topical ocular timolol in elderly patients.

BACKGROUND: Systemic adverse effects of ocular timolol therapy are due to absorption of the drug from the eye into the systemic circulation. Elderly patients are frequently more susceptible to side effects than younger patients. This study was conducted to evaluate the plasma kinetics and antagonist activity of ocular timolol in elderly patients. METHODS: Plasma kinetics and antagonist activity of timolol were studied in 12 patients scheduled for extracapsular cataract extraction and intraocular lens implantation. The patients received 40 microliters of 0.25% timolol into the lower cul-de-sacs of each eye. Blood samples were collected over a period of 12 h and plasma concentrations of timolol were analyzed using a radioreceptor assay. The corresponding ex vivo beta 1- and beta 2-receptor occupancies were calculated using radioligand binding techniques. RESULTS: Timolol was absorbed rapidly into the systemic circulation and occupied on average up to 68% of beta 1-receptors and up to 87% of beta 2-receptors. The beta 1- and beta 2-receptor occupancy decreased slowly and was on average 38% and 64%, respectively, 12 h after the single dose. The calculated mean area under concentration-time curve of timolol in plasma was 10.28 ng/ml per hour and the mean half-life was 4.8 h. Both values were about twice as high as those found in healthy young volunteers following an intravenous 0.25-mg dose of timolol. CONCLUSIONS: In elderly patients the beta-receptor antagonist effect of ocular timolol after a single dose is strong and long-lasting. This finding may explain the frequent reported systemic side effects of ophthalmic timolol.

Absorption↗

PubMed1994

Receptor binding assays in analysing the bioavailability and pharmacodynamic bioequivalence of active drug moieties. A study of metoprolol.

The bioavailability and pharmacodynamic bioequivalence of a conventional and an experimental sustained-release formulation of 100 mg metoprolol tartrate were studied in a randomised cross-over study in seven healthy volunteers by assessing over 24 h the plasma kinetics of R,S-metoprolol, its beta 1-adrenoceptor binding component, and by determining the extent to which the active drug moiety in plasma occupied rabbit lung beta 1- and rat reticulocyte beta 2-adrenoceptors. The formulations differed markedly in their kinetic characteristics: the peak plasma concentration (Cmax) of R,S-metoprolol after administration of the conventional formulation was 140 ng.ml-1, (n = 7) and it was approximately one-third of that after the sustained-release formulation, 49 ng.ml-1, (n = 6); the AUC0-24 h-values for the formulations were 700 and 310 ng.h.ml-1, respectively. The Cmax for the beta 1-adrenoceptor binding component of metoprolol was 180 ng.ml-1 (n = 7) after administration of the conventional, and 74 ng.ml-1 after administration of the sustained-release formulation. The corresponding AUC0-24 h-values for the receptor binding component were 920 and 470 ng.h.ml-1 (n = 7). Thus, the kinetic differences between R,S-metoprolol and the beta 1-receptor binding component were considerable and they were affected by the type of formulation. In general, after administration of the sustained-release formulation, the percentage beta 1- and beta 2-adrenoceptor occupancy of metoprolol in plasma was 5-15% less than after administration of the conventional formulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-1 Receptor Antagonists↗

PubMed1994

The effects of transdermal scopolamine on autonomic nervous activity during sleep.

We studied the effect of transdermally applied scopolamine (scopolamine-TTS) on autonomic nervous activity during sleep. The double-blind, randomized, crossover study was carried out in six healthy male volunteers by applying 1.5 mg scopolamine-TTS or placebo patch on the retroauricular skin and by monitoring heart rate, cardiac ballistogram, respiration and body movements by using electrocardiogram and static charge sensitive bed. Scopolamine did not decrease the time the subjects desired to sleep (516 min after TTS, 511 min after placebo) or the number of body movements of 3-5 s duration the subjects spontaneously performed during sleep (47 after TTS, 58 after placebo). No adverse effects of scopolamine were reported spontaneously. Scopolamine-TTS slowed the mean heart rate during quiet sleep from 53.2 to 44.9 beats.min-1, and increased the duration of bradycardia in response to body movements (MIB-reflex) from 12.5 to 14.7 s with a significant difference between scopolamine and placebo effects. The bradycardias were not associated with disturbances in cardiorespiratory or central nervous system functions. The cardiac vagomimetic action of scopolamine-TTS could be explained by low plasma drug concentrations (175 pg/ml) primarily blocking only neuronal inhibitory prejunctional muscarinic receptors which regulate acetylcholine release from the autonomic ganglia and parasympathetic nerve-endings. Because of the central role of acetylcholine in the physiological regulation of sleep, the effect of scopolamine-TTS on sleep merits further investigations.

Administration, Cutaneous↗

PubMed1994

Chronic alcohol intake and carbachol-induced acute pancreatitis in the rat.

Alcohol-induced changes in cholinergic and pancreozymin pathways regulating exocrine pancreatic secretion have been proposed to play a crucial role in the pathogenesis of acute alcoholic pancreatitis. In the present study we investigated the role of chronic alcohol intake in an experimental acute pancreatitis induced in rats by cholinergic hyperstimulation. Chronic alcohol intake interfered with the function of rat pancreatic muscarinic receptors in carbachol-induced acute pancreatitis. However, chronic alcohol intake did not sensitize the experimental animals to cholinergic hyperstimulation. Whether this increased resistance at the level of pancreatic muscarinic receptors contributes to acute alcoholic pancreatitis is discussed in the present article.

Acute Disease↗