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Results for “PARASYMPATHOMIMETICS”

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At least 19 recordsLinked to original sources

PubMed2002

Combined use of tertiary amine parasympathomimetics with a quaternary amine parasympatholitic--a new perspective to use parasympathomimetic drugs for systemic analgesia.

The interactions on antinociception between a muscarinic agonist arecoline (arec), an anticholinesterase physostigmine (physo) which both cross CNS, and a peripherally acting antimuscarinic hyoscine-N-butyl bromide (hyo), were assessed by tail flick test in mice. All drugs were administered intraperitoneally (i.p.). While hyoscine-N-butyl bromide (0.15 and 4.00 mg/kg, i.p.) did not produce antinociception, physostigmine salicylate (0.3 mg/kg, i.p.) and arecoline hydrobromide (8.00 mg/kg, i.p.) exerted significant antinociceptive effect. In combined applications, physo + hyo (0.075 + 0.15; 0.15 + 0.30; 0.30 + 0.60 mg/kg) and arec + hyo (1.00 + 0.50; 2.00 + 1.00; 4.00 + 2.00; 8.00 + 4.00 mg/kg), respectively, produced significant antinociception and the tail flick latencies produced by physo 0.30 + hyo 0.60 mg/kg and arec 8.00 + hyo 4.00 mg/kg were not significantly different from those of physo 0.30 mg/kg and arec 8.00 mg/kg, respectively, showing that hyo did not antagonise the antinociceptive effects of physo and arec. We believe that combining an centrally acting cholinergic drug applied systemically with a peripherally acting (quaternary amine) antimuscarinic compound might be used as an effective analgesic in clinical practice.

Amines↗

PubMed1977

Uropharmacology: IV. Parasympathomimetic drugs.

Parasympathomimetic drugs include (1) acetylcholine and several synthetic choline esters and related derivatives, and (2) naturally occurring cholinomimetic alkaloids and certain related synthetic compounds. Pharmacology of acetylcholine, the prototype parasympathomimetic, is presented, as well as an introduction to other parasympathomimetic drugs and choline esters.

Acetylcholine↗

PubMed1997

The effect of topical parasympathomimetics on corneal epithelial healing in rabbits.

Corneal wound healing is an important process that involves interaction between the different corneal cell layers, growth factors, and environmental conditions. More powerful therapies for the treatment of delayed epithelial wound healing are still being proposed. The objective of this study is to investigate the effects of the direct-acting parasympathomimetic agents on the healing process of corneal epithelium in rabbits. The corneal epithelial defects, 10 mm in diameter, were created in 32 eyes of 16 island rabbits by combination of chemical debridement using n-heptanol and mechanical scraping. Animals were randomly divided into four groups. Groups 1, 2 and 3 were treatment groups; each group consisted of four rabbits (8 eyes). The animals in these groups were treated with topical 1% acetylcholine (ACh), 2% pilocarpine, and 0.75% carbachol drops respectively. In group 4, four rabbits (8 eyes) were used as control group and left for spontaneous healing. The length and area of the defect were measured at days 3,6,9,12,15,18 and 22 after wounding. Areas of the photographically documented fluorescein-stained defects were measured by planimetry. All eyes in the treatment groups reepithelialized completely. The duration for reepithelialization in Groups 1 and 2 was 12 days, and 18 days for Group 3. In the control group reepithelialization occurred within 22 days. The healing rates of corneal epithelium were statistically significantly faster in all treatment groups as compared with the control group at all times (p=0.0001 to 0.0279). Although the rates of wound healing varied, all of the parasympathomimetics used in the present study were found to facilitate wound healing. Our results indicate that direct-acting cholinergic agents, especially ACh and pilocarpine, may have an important therapeutic role in the treatment of severe corneal epithelial injury.

Acetylcholine↗

PubMed1977

Uropharmacology: v. choline esters and other parasympathomimetic drugs.

Various parasympathomimetic drugs are discussed, including the choline esters, bethanechol, carbachol, methacholine chloride, and furtrethonium. Other cholinomimetic agents include muscarine, muscarone, arecholine, and pilocarpine. Anticholinesterase agents inhibit or inactivate acetylcholinesterase enzyme and thus result in a prolonged stimulation of cholinergic receptors by endogenous ACh. Bethanechol is the most widely used parasympathomimetic drug in the United States. Its action is mainly muscarinic with activity largely confined to the urinary bladder and to a lesser degree the gastrointestinal tract. It can be administered only subcutaneously or orally, and adequate dosage is necessary for a successful response.

Animals↗

PubMed1977

Parasympathomimetic action of scorpion venom on the cardiovascular system.

Although the precise mechanism of the cardiovascular effects in man evoked by the venom of the yellow scorpion has yet to be completely elucidated, previous studies indicate that excessive adrenergic activity is present in many of the cases. This report describes two patients in whom yellow scorpion sting was followed by bradyarrhythmia with varying degrees of atrioventricular block which promptly regressed after the administration of atropine; this is consistent with a direct parasympathomimetic effect of the venom or with a central effect producing increased vagal tone. It is suggested that the cardiovascular actions of the venom may represent a wide spectrum of effects on the autonomic nervous system, ranging from the predominantly sympathomimetic to the predominantly parasympathomimetic.

Adult↗

PubMed2003

Role of specific muscarinic receptor subtypes in cholinergic parasympathomimetic responses, in vivo phosphoinositide hydrolysis, and pilocarpine-induced seizure activity.

Muscarinic agonist-induced parasympathomimetic effects, in vivo phosphoinositide hydrolysis and seizures were evaluated in wild-type and muscarinic M1-M5 receptor knockout mice. The muscarinic agonist oxotremorine induced marked hypothermia in all the knockout mice, but the hypothermia was reduced in M2 and to a lesser extent in M3 knockout mice. Oxotremorine-induced tremor was abolished only in the M2 knockout mice. Muscarinic agonist-induced salivation was reduced to the greatest extent in M3 knockout mice, to a lesser degree in M1 and M4 knockout mice, and was not altered in M2 and M5 knockout mice. Pupil diameter under basal conditions was increased only in the M3 knockout mice. Pilocarpine-induced increases in in vivo phosphoinositide hydrolysis were completely absent in hippocampus and cortex of M1 knockout mice, but in vivo phosphoinositide hydrolysis was unaltered in the M2-M5 knockout mice. A high dose of pilocarpine (300 mg/kg) caused seizures and lethality in wild-type and M2-M5 knockout mice, but produced neither effect in the M1 knockout mice. These data demonstrate a major role for M2 and M3 muscarinic receptor subtypes in mediating parasympathomimetic effects. Muscarinic M1 receptors activate phosphoinositide hydrolysis in cortex and hippocampus of mice, consistent with the role of M1 receptors in cognition. Muscarinic M1 receptors appear to be the only muscarinic receptor subtype mediating seizures.

Animals↗

PubMedDate not supplied

Effects of the parasympathomimetic drug methacholine and its antagonist atropine on mucociliary activity.

The effect on the mucociliary (m.c.) activity of the parasympathomimetic drug methacholine and its antagonist atropine was studied with the aid of a newly developed animal test model, designed for evaluating the effect of pharmacological substances on the m.c. wave frequency. Methacholine i.a. (0.01-2 micrograms/kg) was found to give a dose-dependent acceleration of the m.c. wave frequency, and the threshold dose 0.03 +/- 0.02 (+/- S.D.) micrograms/kg is suggested to be within physiological limits. The anticholinergic drug atropine i.a. (0.05-0.5 mg/kg) did not influence the basal m.c. wave frequency, but a dose of 0.2 mg/kg reduced or abolished the responses to methacholine (0.05-2 micrograms/kg). These results indicate that the basal m.c. activity functions independently of parasympathetic activity in anesthetized animals, that parasympathomimetic drugs influence the m.c. activity and that the effects of these drugs can be reduced or blocked by atropine.

Animals↗

PubMed2002

A signal transduction pharmacodynamic model of the kinetics of the parasympathomimetic activity of low-dose scopolamine and atropine in rats.

We used a novel pharmacokinetic-pharmacodynamic (PK-PD) approach that had been applied for signal transduction kinetics to investigate the kinetics of the parasympathomimetic effect of scopolamine and atropine in rats. The parasympathetic tone was assessed by continuous measurement of the power of the high frequency band (HF) of electrocardiogram (ECG) R-R intervals obtained by power spectral analysis (PSA) of heart rate variability (HRV). To overcome the inherent noise of the HRV-HF data and to quantitatively identify temporal changes in the autonomic tone, a new approach of stepwise regression of the cumulative HF data was applied. The elevation of the parasympathetic tone occurred after a significant lag time (>70 min) following scopolamine administrations [0.25 and 0.5 mg/kg intravenous (iv) bolus or infusion over 100 min], followed by a gradual return to the baseline levels. A similar lag time in parasympathetic stimulation was observed following iv bolus administration of atropine (0.1 mg/kg). The plasma drug concentration versus time data were linked to the response versus time data using a signal transduction pharmacodynamic model that was fitted simultaneously to all four experimental data sets. This PK-PD model resolved the significant discrepancy between the concentration versus time and the response versus time patterns and successfully described the kinetics of the parasympathetic stimulation obtained for different drugs and different rates of administration. This work paves the way for further PK-PD preclinical investigations in this field.

Animals↗

PubMed1994

Cholinergic dysfunction in Shy-Drager syndrome: effect of the parasympathomimetic agent, bethanechol.

To determine the frequency, severity and organ distribution of cholinergic dysfunction in the Shy-Drager syndrome, eleven patients were prospectively studied. In addition to documenting adrenergic insufficiency, a battery of twelve tests was employed to assess cholinergic function. Six tests demonstrated pupillary, lacrimal, salivary, urinary bladder, sexual and sudomotor dysfunction in the majority of patients. Cardiac vagal function as studied by the heart rate response to deep breathing, the Valsalva manoeuvre, cold face test, apnoeic facial immersion and atropine test was affected in all patients. Oesophageal motility was abnormal in six patients. Cholinergic dysfunction in patients with the Shy-Drager syndrome was widespread but of variable severity and distribution. Subcutaneous administration of the parasympathomimetic agent bethanechol demonstrated hyperresponsiveness of lacrimal, salivary, oesophageal, bowel, bladder and sudomotor functions. It is suggested that the Shy-Drager syndrome is primarily a preganglionic cholinergic disorder with transsynaptic degeneration accounting for the development of postganglionic cholinergic as well as adrenergic dysfunction.

Aged↗

PubMed1975

Abnormal secretory response to parasympathomimetic and sympathomimetic stimulations from the submaxillary gland of rats treated with reserpine.

Rats treated with 0.5 mg/kg of reserpine per day for 7 days were anesthetized and submaxillary saliva was collected and analyzed for Na+, K+, Ca++ and protein concentrations. Salivary secretion was elicited by i.p. injections of carbamylcholine (50-100 mug/kg), phenylephrine (5 mg/kg) and isoproterenol (10 mg/rat). Saliva was also collected from untreated controls. Submaxillary glands were excised from both groups of animals at the termination of the secretory response, homogenized and analyzed. Glands from other animals were removed in the resting state and similarly processed. Pretreatment with reserpine resulted in decreased volumes of salvia and in elevated salivary concentrations of Ca++ and protein. Saliva from the reserpine-treated animals secreted in response to carbamylcholine had higher concentrations of Na+ and K+ than control saliva, particularly at the low rates of flow. Saliva secreted after stimulation with the two sympathomimetic secretagogues had lower concentrations of these two ions. Resting glands from the treated animals showed significant elevations in protein and Ca++ content and a significant decrease in K+ content. At the end of the secretory response to the three secretagogues, glands from treated animals showed a significantly higher Na+ content and a significantly lower K+ content than control glands. It is concluded that pretreatment with reserpine alters the secretory response of the rat submaxillary gland to both parasympathomimetic and sympathomimetic stimulation. This alteration results from a toxic lesion caused by reserpine in the salivary cells, which involves changes in their permeability to ions and in their energy resources. These in turn, result in an abnormal stimulus-secretion coupling mechanism. The possibility that the toxic lesion is related to alterations in Ca++ homeostasis is discussed.

Animals↗

PubMed1976

Potassium release from the rat submaxillary gland in vitro. II. Induction by parasympathomimetic secretagogues.

The kinetics of K+ release from an in vitro system of rat submaxillary gland slices were studied after stimulation with parasympathomimetic secretagogues. The slices were incubated at 37degreesC in an oxygenated, enriched Krebs-Ringer bicarbonate medium in the presence and in the absence of Ca++ and of ouabain and, in some experiments, in the presence of the specific antagonists atropine (5 x 10(-6) and 2 x 10(-5) M), phentolamine (2 x 10(-5) M) or propranolol (2 x 10(-5) M. K+ release was elicited by the addition of acetylcholine (2 x 10(-5) M), pilocarpine (2 x 10(-5) M) and carbamylcholine (10(-9) to 2 x 10(-5) M). The results demonstrate that: 1) The selective stimulation of cholinergic receptors induces a rapid net release of K+ from the slices. After 10 minutes of incubation, the percent K+ released after a 2 x 10(-5) M dose of each of the three secretagogues was, respectively, 20.8%, 15.5%, and 19%. 2) The response to carbamylcholine does not occur when Ca++ is absent from the medium and is blocked by atropine but not by phentolamine or by propranolol. Atropine (5 x 10(-6) M) causes a 17-fold shift to the right on the dose-response curve to carbamylcholine. 3) The magnitude of K+ release is the ratio of two opposing mechanisms, a passive efflux and an active reuptake. The latter depends on the activity of the ouabain-sensitive Na+-K+-adenosine triphosphatase. 4) The sensitivity of the slice system to carbamylcholine seems to be greater than that to norepinephrine in terms of net K+ release after equimolar doses of 2 x 10(-5) M and also in terms of the dose required to induce a half maximal passive K+ efflux. However, the maximal passive K+ efflux is similar after both types of secretagogue and amounts of approximately 45% of the K+ present in the slices.

Acetylcholine↗

PubMed1992

Parasympathomimetic activity of salpantiol. A new cyclitol from Salpianthus arenarius.

A new cyclitol was isolated using the flowers of the Salpianthus arenarius, and its chemical structure was determined (2-methoxy-5hydroxymethyl cyclopentane-1,3,4-triol). The contractile effects of acetylcholine (Ach), Atropine, Pilocarpine, Adrenaline and Cyclitol were studied in rat ileum. Such cyclitol proves to have parasympathomimetic activity.

Animals↗

PubMed1962

Early diagnosis of leprosy by study of the sweat response to iontophoresis with parasympathomimetics.

The final aim of any leprosy control campaign is the eradication of the disease, or at least its reduction to a point where it no longer constitutes a major public health problem. The only possible ways of achieving this end are, firstly, through intensive case-finding and, secondly, through mass treatment.For obvious reasons diagnosis must be made at the earliest possible moment, which is not always easy by ordinary methods. Thus any technique to improve early diagnosis deserves full study. Observation of the sweat response to iontophoresis using parasympathomimetic drugs seems an easy and objective method of detecting leprosy skin lesions; it may therefore constitute a valuable step forward in the improvement of leprosy control.

Early Diagnosis↗

PubMed1989

The use of anxiolytic and parasympathomimetic agents in the treatment of postoperative urinary retention following anorectal surgery. A prospective, randomized, double-blind study.

Approximately 30 percent of patients undergoing anorectal surgery will develop acute urinary retention. The cause of this complication is poorly understood. Anxiety, anal distention, bladder distention as a result of vigorous hydration during surgery, and reflex inhibition of the urinary bladder detrusor muscle secondary to pain have been postulated as contributing factors. A four-armed prospective, double-blind, randomized trial was carried out to determine whether an anxiolytic agent (midazolam, 5 mg intramuscularly) and/or a parasympathomimetic agent (bethanechol, 10 mg subcutaneously) reduce the incidence of postoperative urinary retention following anorectal surgery. One hundred thirty-two patients (ages, 18 to 50 years), in acute urinary retention 6 to 12 hours following anorectal surgery, were enrolled. Sixty-nine percent of patients responded to bethanechol. Side effects were minimal. Midazolam alone had no effect on retention. Bethanechol and midazolam in combination resulted in less retention than midazolam and a placebo (P less than 0.05). Bethanechol alone was better than a placebo (P less than 0.002). Mean intraoperative intravenous fluid volume for the entire study group was 900 cc. Initial postoperative urinary volumes of patients who failed the treatment protocol were significantly higher than in those responding to bethanechol (mean of 527 cc vs. 241 cc, P less than 0.001). The use of an anxiolytic agent was not effective in the treatment of postoperative urinary retention. Bladder distention may increase the incidence of urinary retention. Bethanechol, in a dose of 10 mg subcutaneously, significantly lowered the incidence of postoperative urinary catheterization and should be considered as initial treatment of postoperative urinary retention following anorectal surgery.

Acute Disease↗

PubMed1965