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At least 829 records · Page 46Linked to original sources
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↗
PubMed1989

[An artificial salivary gland. Indications. Technical note concerning installation].

Idiopathic or iatrogenic aptyalism is responsible for disabling odontostomatological symptoms and constitutes a predisposing factor for bucco-dental complications. Drug treatment designed to stimulate the salivary parenchyma is doomed to failure in cases of severe, irreversible alteration of the glandular acini. The only available treatment is palliative consisting of buccal artificial salivation. Two modalities of endobuccal administration of artificial saliva have been developed: prosthesis-reservoir and "artificial salivary gland". The "artificial salivary gland" consists of a system connecting an external reservoir to the buccal cavity via a catheter implanted over part of its path. The artificial saliva stored in the reservoir is advanced mechanically as far as the mouth where it is released according to an adjustable flow rate. The insertion of a medical silicone catheter is an outpatient procedure with a simple postoperative course. Under normal conditions, one millilitre of saliva solution per hour is sufficient to ensure satisfactory humidification of the buccal mucosa. Dysfunction of the system is generally due to a mechanical problem and any consequent alterations are treated as required. The indications for "artificial salivary gland" must be reserved to semi-urgent cases with severe aptyalism and as a therapeutic relay in the context of global management of the aptyalic patient. This new modality of administration could be extended to other diseases requiring endobuccal drip treatment.

Artificial Organs↗
PubMed1989

Pharmacological profile of moclobemide, a short-acting and reversible inhibitor of monoamine oxidase type A.

The novel antidepressant moclobemide is a reversible inhibitor of monoamine oxidase (MAO), preferentially of type A. Moclomide was active in three animal models considered predictive for antidepressant activity: 1) it prevented dose-dependently akinesia and blepharospasm induced in mice and rats by Ro 4-1284, a short-acting amine releasing agent. Prevention of akinesia by moclobemide also depended upon the dose of Ro 4-1284. For comparison also, effects of cimoxatone, harmaline, tranylcypromine and clorgyline are presented: 2) in cats, it selectively and dose-dependently suppressed rapid eye movement sleep without disturbing the sleep-wakefulness cycle; and 3) in the behavioral despair test in mice, it decreased the immobility score to a similar degree as amitriptyline or imipramine. In addition, moclobemide potentiated 5-hydroxytryptophan-induced stereotypies in rats with a potency similar to cimoxatone and with a duration of action of less than 24 hr. Moclobemide had almost no effect on the spontaneous behavior in mice, rats, cats and monkeys. Only in higher doses, marginal sedation and slight impairment in motor performance were seen. Moclobemide did not prevent pilcarpine-induced salivation in mice, demonstrating the absence of anticholinergic activity. Blood pressure and heart rate of freely moving, spontaneously hypertensive rats were only slightly decreased for less than 3 hr. Moclobemide moderately potentiated the pressor effect of p.o. tyramine in rats. In conclusion, the reversible MAO inhibitor moclobemide is active in animal models sensitive to all major drugs used in the treatment of depression. In contrast to imipramine-like antidepressants, it lacks anticholinergic activity and it differs from classic MAO inhibitors by potentiating only weakly the pressor effect of p.o. tyramine.

2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-↗
PubMedDate not supplied

[Food conditioned reflexes in dogs during activation and blockade of the cholinoreactive system of the amygdala].

By means of chemical stimulation of subcortical structures it has been found that the cholinoreactive system of the basolateral part of amygdala is involved in realization of secretory component of alimentary conditioned reactions and takes no direct part in accomplishment of the instrumental component. Activation of the cholinoreactive system of the amygdalar basolateral part has an inhibitory effect and the blockade has an activating effect on the realization of the secretory component of alimentary conditioned reactions. A change in characteristics is observed of the differentiation inhibition and of the correlation of conditioned salivation in response to various stimuli presented in a stereotype order.

Acetylcholine↗
PubMed1988

[Treatment of Sjögren's syndrome with protease inhibitors].

The authors reported the results of therapy of 28 patients with primary and secondary Sjogren's syndrome by iv injections of protease inhibitors (contrykal and trasylol). Findings of clinical and laboratory tests showed a significant increase in salivation and lacrimation. The elimination of concomitant oral candidosis raised the efficacy of treatment of xerostomia in many patients.

Adult↗
PubMed1987

Regional differences in receptor reserve for analogs of oxotremorine in vivo: implications for development of selective muscarinic agonists.

The muscarinic actions of several analogs of oxotremorine were compared in the mouse. Compounds such as AKS 19 and BM 5 having low intrinsic efficacy (partial agonists) differentiated between centrally mediated muscarinic effects as they, like oxotremorine, were potent in producing analgesia and hypothermia but did not produce tremor. Instead they antagonized oxotremorine-induced tremor. They resembled oxotremorine in their ability to stimulate salivary secretion. Excellent correlations were found between the various muscarinic effects measured in vivo and spasmogenic activity on the guinea pig ileum and between tremorolytic potency and affinity for ileal muscarinic receptors. The results suggest that there are regional differences in the receptor reserve for muscarinic agonists that may affect in vivo responses to partial agonists in a qualitative manner. Responses to more efficacious agonists such as oxotremorine are affected only quantitatively by such differences. Efficacious agonists appeared to have a large receptor reserve with respect to salivation, analgesia and hypothermia, whereas their receptor reserve for the tremor response was lower. The possibility is raised of achieving selective muscarinic actions, even in the absence of distinct subtypes of muscarinic receptors, by exploiting regional differences in receptor density, in the efficiency of receptor-effector coupling and in endogenous levels of acetylcholine.

Analgesia↗
PubMed1986

An atropinized heat-stressed rat model: dose response effects and pharmacokinetics.

Atropine and other anticholinergic drugs are widely used in common medications and in the treatment of organophosphate poisoning. Man dissipates heat by the evaporation of sweat. Analogously, rats spread saliva over their bodies for evaporative cooling. Atropine inhibits both sweating and salivation. Therefore, we sought to quantitate the effects of atropine in our rat heatstroke model. While heat-stressing adult male rats of 500 or 250 g at 41.5 degrees C, we measured the effects of i.v. atropine (10-4000 micrograms X kg-1) on the following: heating rate (HR), % wt loss (saliva production), and fecal loss (intestinal motility). HR (degree C X min-1) was the most sensitive index of drug activity with a 200 micrograms X kg-1 dose (equivalent to 2 mg in man for organophosphate poisoning) eliciting an increased HR from 0.022 degrees C (saline) to 0.087 degrees C X min-1 (atropine). Atropine (200 micrograms X kg-1) increased HR even if administered 3 h prior to heat exposure. Large (500 g) rats showed an increase in HR with 25 micrograms X kg-1 of atropine, but 250 g rats required 50 micrograms X kg-1. This model could be used to assess the relative effects of other anticholinergic drugs and as a non-dehydrated heatstroke model.

Animals↗
PubMed1986

Central and autonomic nervous system side effects of ketanserin.

A placebo controlled, randomized, double-blind cross-over study was carried out in 7 healthy volunteers in order to study the central and autonomic nervous system side effects of ketanserin in comparison to clonidine. Psychometric performance was assessed as well as electroencephalographic recordings (EEG), saliva production, mean arterial blood pressure (MAP) and pulse rate under placebo conditions (P, 10 ml saline), following 0.15 mg/kg ketanserin or 2 micrograms/kg clonidine i.v. administration. The sedation index as well as the deceleration of EEG frequencies clearly expressed sedation following both, ketanserin and clonidine. Saliva production was significantly decreased by ketanserin (p less than 0.05) and clonidine (p less than 0.01), respectively. MAP was only very slightly reduced by ketanserin, while clonidine caused a small but significant decrease (p less than 0.0001). The pulse rate changes did not reach a clinically important extent. Thus, sedation as main central nervous system side effect and reduction in salivation as autonomic nervous system side effect of ketanserin could be clearly quantified in comparison to placebo and clonidine.

Adult↗
PubMedDate not supplied

Deltamethrin infusion into different sites in the neuraxis of freely-moving rats.

A comparison of signs induced by deltamethrin infusion at 3 sites within the neuraxis was made in freely-moving rats. Cannulae were placed prior to experiment into either lateral ventricle, cisterna magna or spinal subarachnoid space and animals allowed to recover. Deltamethrin was active at all levels of the neuraxis in a dose dependent manner. All signs induced by intraperitoneal deltamethrin administration, except profuse salivation and choreoathetosis, were generated by direct infusion of the compound into the CNS. In addition other signs developed which cannot be observed following systemic administration. They seemed to reflect a local disturbance in function around each injection site. With regard to the major symptom of choreoathetosis associated with systemic deltamethrin administration, the results suggest that for such a complex response to develop, a more global activation at many levels of the neuraxis (and possibly in the periphery) is required.

Animals↗
PubMed1985

Factors associated with the acceptance of sugar and sugar substitutes by the public.

Acceptance is described in both market and sensory research terminology and recent developments in the fields of applied psychology and physiology are examined for their pertinence to public acceptance of sucrose and its substitutes. Information on the function of sucrose in foods other than beverages is presented with emphasis on salivation as an acceptance factor and attention is drawn to its possible dental significance. Distinctions are made between the sweetening and bulking properties of sucrose and sugar substitutes. Factors having a bearing on the acceptance of sweet foods and the determination of their optimal sugar content are described in detail. While major decreases in sucrose intake in the US resulted from high-fructose corn-sweetener usage in soft drinks, no evidence is yet available to suggest that the use of sugar substitutes of the intense artificial sweetener type has caused any decrease in ordinary sugar consumption. Neither is the consumption of polyols (sorbitol, mannitol, xylitol) high enough in confectionery categories to cause any discernible decrease in sugar usage. The evidence suggests not so much that sugar substitutes may have stopped the growth in sucrose usage, but that new product categories such as diet foods and "sugarless' confections may have been created. These categories were never available to fermentable carbohydrate sweeteners and equivalence in acceptance to sucrose-sweetened products was not an important factor in their growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1985

Oxotremorine-induced cholinergic syndrome: modifications by levodopa and/or oral cytidine diphosphocholine.

A peripheral and cerebral cholinergic syndrome was induced in mice by oxotremorine administration; pretreatment orally with cytidine diphosphocholine (CDP-choline) does not potentiate this syndrome and even antagonizes oxotremorine-induced salivation. Levodopa antagonizes the oxotremorine-induced cerebral symptoms (akinesia + tremor); however this antagonism disappears when mice are chronically pretreated orally with CDP-choline, confirming the action of CDP-choline on dopaminergic pathways. The proven efficacy of CDP-choline in Parkinsonism could then be mediated by a hypersensitivity of some cerebral dopamine receptors, and not by a direct stimulating effect of the striatal dopaminergic receptors.

Administration, Oral↗
PubMed1985

Trigger activation of the paradoxical salivatory response to atropine in the parasympathetically denervated human parotid gland.

The author describes a specific intermediate condition of the response to atropine during the 2nd stage of denervation of the human parotid gland. Of the entire cohort of 110 subjects, some 20 subjects have been observed systematically. They demonstrated an extremely intense atropine salivation that followed an additional trigger activation, namely food or acid irritation of the mouth mucosa. The initial phase of such a stimulation was characterized by a sharp, explosive increase in secretion. The following conclusions have been inferred: (1) in the 2nd stage of parasympathetic denervation of the human parotid gland, there emerges a specific intermediate condition of 'readiness' for an extremely intense paradoxical salivatory response to atropine and other cholinolytics; (2) the pre-start 'readiness' state may be activated by means of adding a trigger signal followed by an explosive occurrence of abundant secretion; (3) only food or acid irritation, even to a minimal extent, of the mouth cavity may serve a specific trigger signal; (4) a stable state of this trigger readiness has been observed in 20 subjects for years, while in other subjects it has been observed as a transitory event between the 1st and the 3rd stages of denervation and during the regression of symptoms in the rehabilitation period; (5) suggestions have been made concerning the trigger activation mechanism of the atropine salivatory paradox and the evolutionary, model and clinical significance of the events described.

Atropine↗
PubMed1972

Impairment of salivary reflexes after lateral hypothalamic lesions in dogs.

The effects of lateral hypothalamic lesions on salivary conditioned and unconditioned reflexes were investigated on seven dogs. Subsequent to the operation during the period of aphagia and hypophagia a total lack (6 dogs), or a decrease (1 dog) of conditioned salivary reaction was found. Strong diminution of unconditioned reactions and intertrial salivation were observed. At the end of the observation period (7 months) the conditioned and unconditioned salivary reflexes were still diminished reaching levels of 12-54 percent and 35-75 percent respectively in comparison with the pre-operative period. The mechanism of the impairment of salivary reactions was discussed.

Animals↗
PubMed1984

Carboxyl-terminal tripeptidyl hydrolysis of substance P by purified rabbit lung angiotensin-converting enzyme and the potentiation of substance P activity in vivo by captopril and MK-422.

The hydrolysis of substance P is catalyzed by purified rabbit lung angiotensin-converting enzyme (peptidyldipeptide hydrolase, EC 3.4.15.1). The kcat/Km for the reaction at 37 degrees is 3.3 +/- 0.3 X 10(3) M-1 sec-1, which is 60 times less than that which has been reported for the hydrolysis of angiotensin I. The initial site of hydrolysis is the antipenultimate peptide bond, which generates the tripeptide amide (Gly-Leu-Met-NH2). This hydrolysis is inhibited by the angiotensin-converting enzyme inhibitors captopril, MK-422, and EDTA, and is dependent on the concentration of chloride ion. Both captopril and MK-422 potentiate the substance P-induced stimulation of salivation in rats. Thus, angiotensin-converting enzyme may be one of the enzymes that degrade substance P in vivo.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1982

[The assessment of the function of the nervus intermedius by means of functional salivary gland-scintigraphy].

Using functional scintigraphy of the salivary glands, the function of the nervus intermedius can be assessed by estimating excretory quotients for both submandibular glands. This method is preferred to the standard salivation test method of Magielski and Blatt, despite a minimal exposure of the patient to radiation from the injected Natriumpertechnetat. The technical course of this investigation, along with the indications for its use, will be presented.

Facial Nerve↗
PubMedDate not supplied

[Conditioned reflexes following unilateral damage to the premotor cortex and the dorsal portion of the head of the caudate nucleus in dogs].

The study was carried out on dogs by the secretory-motor method with a two-side reinforcement. Simultaneous and unilateral lesion of the premotor cortex and of the dorsal part of the caudate nucleus head brought about prolonged disturbances of the vegetative components (pulse and respiratory rate) and in the choice of the side of food reinforcement. The change in the magnitude of conditioned salivation, latencies of secretion and motor reaction was temporary, and by the end of the third postoperative period their initial magnitudes were restored. The duration of the disturbances of higher nervous activity depended on the localization and extent of lesion of the caudate nucleus head. Tests were made with chlorpromazine and caffeine before and after the lesion of the brain structures. The tests in the postoperative period revealed latent disturbances in the dog higher nervous activity. It is assumed that the premotor cortex and the dorsal part of the caudate nucleus head are one of the sub-systems involved in the regulation of vegetative, somatic components of unconditioned behaviour and in the analysis of conditioned stimuli.

Animals↗
PubMed1984

Pharmacological properties of two amino esters of diphenylpropanoic acid.

N, N-Diethylaminoethyl ester and 3-quinuclidinyl ester of 2, 2-diphenylpropanoic acid (compound 1 and 2, respectively) were prepared and pharmacologically evaluated in vitro and in the intact animal. Both compounds attenuated the effects of increasing doses of ACh in the isolated rat ileum (pA2 = 8.40 and 8.55, respectively). These effects were comparable to that of atropine (pA2 = 8.73). The duration of methacholine-induced salivation in male Swiss-Webster mice was significantly decreased by compound 2 but not by compound 1. Cardiorespiratory studies in adult male Sprague-Dawley rats revealed that both compounds shifted the dose-response curves to methacholine in terms of arterial blood pressure, heart rate and respiration upwards; indicative of cholinergic blockade. The observed pharmacological differences between the two compounds may be attributed to apparent in vivo hydrolysis of compound 1 by esterases.

Acetylcholine↗
PubMed1984

Antagonism of pancuronium neuromuscular blockade in halothane-anesthetized ponies using neostigmine and edrophonium.

Efficacy of neostigmine (0.04 mg/kg of body weight) and edrophonium (1 mg/kg), as antagonists for pancuronium neuromuscular blockade in halothane-anesthetized ponies, was evaluated. Neostigmine and edrophonium were satisfactory antagonists, with edrophonium having a significantly (P less than 0.01) more rapid onset of action than did neostigmine. Muscarinic activity of neostigmine and edrophonium was also evaluated. Neither antagonist was administered with atropine. Gastrointestinal effects, increased salivation, and increased airway secretions were minimal with edrophonium, but were marked after neostigmine. Blood pressure increased within 1 to 2 minutes of antagonist administration. Heart rate decreased after edrophonium injection, but this occurred after blood pressure increase. Heart rate increased or did not change after neostigmine administration.

Anesthesia, General↗