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PubMed1995

Effects of the cholinomimetic SDZ ENS-163 on scopolamine-induced cognitive impairment in humans.

Scopolamine-induced cognitive impairment was used in healthy men to evaluate the central nervous system activity of the new cholinomimetic SDZ ENS-163. Eighteen subjects were treated in a crossover design with oral placebo/intravenous saline, 50 mg of oral SDZ ENS-163/intravenous saline, oral placebo/0.4 mg of intravenous scopolamine, and 50 mg of oral SDZ ENS-163/0.4 mg of intravenous scopolamine. The administration of placebo with scopolamine caused significant cognitive impairment, as assessed by the Computerized Neuropsychological Test Battery (CNTB), and also decreased salivation and heart rate. In contrast, SDZ ENS-163 with saline had no effect on CNTB scores, increased salivation, and increased heart rate. Despite the observed cholinomimetic effects of SDZ ENS-163 when administered with saline, the changes in CNTB scores, heart rate, and salivation were indistinguishable between placebo/scopolamine and SDZ ENS-163/scopolamine. Thus, 50 mg of oral SDZ ENS-163 has cholinomimetic activity in normal men, but this dose is insufficient to reverse the muscarinic effects of 0.4 mg of intravenous scopolamine.

Adult↗
PubMed1996

The effect of intravenous administration of variable-dose midazolam after fixed-dose ketamine in healthy awake cats.

The effects of intravenous administration of variable-dose midazolam and ketamine (3 mg/kg) were studied in twelve healthy unmedicated cats from time of administration until full recovery. A range of midazolam doses (0.0, 0.05, 0.5, 1.0, 2.0 and 5.0 mg/kg) was chosen, so that beneficial and/or detrimental effects could be documented and the therapeutic window for further study determined. One minute after administration of ketamine, all cats had assumed a lateral position, mostly with head up. Muscle tone was increased (100%), apneustic breathing pattern evident in 92% of cats, chewing without stimulation of the oropharyngeal area was observed in most cats (97%), but most cats did not salivate (87%). At 2.5 min after completion of ketamine injection and 1 min after administration of saline, a similar picture was observed, except that salivation was evident. All cats chewed or swallowed in response to a finger or laryngoscope placed in the oropharyngeal area and, while most cats were not aware of a noxious stimulus to the tail, some cats were aware of a noxious stimulus to the paw. Recovery from ketamine alone was rapid and smooth with cats rolling into sternal recumbency and then cautiously walking with ataxia. Recovery to walking without incoordination was also rapid (< 2 h) and no abnormal behavioural patterns were observed during recovery. Administration of midazolam after ketamine, had beneficial effects and the therapeutic window for midazolam was found to lie between 0.05 mg/kg and 0.5 mg/kg. Administration of any dose of midazolam after ketamine caused a greater proportion of cats to assume a laterally recumbent position with head down compared with ketamine alone, however, the time period of recumbency was only significantly longer with a midazolam dose of 2.0 mg/kg or above. Doses of midazolam of 0.5 mg/kg or above decreased muscle rigidity but did not affect salivation or respiratory pattern observed in cats which received ketamine alone. A significantly greater proportion of cats which received ketamine and midazolam 0.5 mg/kg or above did not swallow in response to a finger or a laryngoscope placed in the mouth compared with that which received ketamine alone. The length of time in which cats did not swallow was only significantly longer at midazolam doses of 1.0 mg/kg and above. At midazolam doses of 0.5 mg/kg or above, the proportion of cats without a nociceptive response to a tail or paw clamp was significantly greater than cats which received ketamine alone. The time period without nociceptive response, however, was not influenced by midazolam administration. The time taken for cats which received ketamine and midazolam 0.05 mg/kg or 0.5 mg/kg to assume sternal position, walk with ataxia, walk without ataxia, behave normally when approached or restrained and recover normal arousal state was not significantly different from cats which received ketamine alone. Ketamine and midazolam 5.0 mg/kg significantly prolonged all recovery times compared with ketamine alone. Unfortunately, a greater proportion of cats which received ketamine and midazolam 0.5 or 5.0 mg/kg exhibited detrimental behavioural effects. These were more likely to be adverse and included restlessness, vocalization and difficulty approaching and restraining cats. In this study, an effect of sex of the cats was found, with male cats taking a significantly longer to recover to sternal recumbency and walk with ataxia, while female cats took longer to recover to a normal arousal state.

Anesthetics, Dissociative↗
PubMed1995

Muscarinic receptor subtypes in the submandibular gland and the urinary bladder of the rabbit: in vivo and in vitro functional comparisons of receptor antagonists.

1. In pentobarbitone-anaesthetized rabbits, the inhibitory effects of muscarinic receptor antagonists with different selectivity profiles were examined on carbachol-evoked submandibular secretion and urinary bladder contractions, and on parasympathetically nerve-evoked secretion. On isolated submandibular gland fragments, the inhibitory effects of the antagonists were studied on carbachol-evoked release of potassium and on the overflow of tritium in response to electrical field stimulation. 2. In vivo, 4-DAMP equipotently inhibited simultaneously carbachol-evoked submandibular secretory and contractile responses of the urinary bladder, while pirenzepine was found to be four times as potent in inhibiting the secretory response compared with the contractile response. 3. The inhibition of carbachol-evoked salivation caused by atropine, 4-DAMP and pirenzepine was as great as their inhibition of parasympathetic nerve-evoked salivation. Methoctramine exerted less inhibitory effect on nerve-evoked salivation than on carbachol-evoked, thus seemingly causing greater presynaptic inhibition. 4. In vitro, pirenzepine was only 30 times less potent in inhibiting carbachol-evoked potassium release than 4-DAMP (pA2, 9.58 vs 8.10). Whereas atropine, 4-DAMP and pirenzepine abolished the overflow of tritium from isolated glands in response to electrical field stimulation, methoctramine increased it. 5. It is concluded that the muscarinic secretory response in the rabbit submandibular gland is exerted via both muscarinic M1 and M3 receptors, while the contractile response of the urinary bladder to muscarinic agonists is exerted via muscarinic M3 receptors. The release of acetylcholine from nerve terminals in the gland can be inhibited via M2 autoreceptors in rabbits.

Animals↗
PubMed2000

Control of salivary secretion by nitric oxide and its role in neuroimmunomodulation.

In many in vivo systems exposure to endotoxins (LPS) leads to the co-induction of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), which is important to the regulation of the function of different systems during infection. In submandibular glands (SMG) neural (n)NOS is localized in neural terminals and in striated, granular convoluted and excretory ducts, endothelial (e)NOS in vascular endothelium and ducts, and iNOS in macrophages and in tubules and ducts. In normal adult male rats, injection of an inhibitor of NOS decreased the stimulated salivary secretion and a donor of NO potentiated it, indicating that NO exerts a stimulatory role. A single high dose of LPS (5 mg/kg, i.p.) induced an increase in NOS activity measured by the 14C-citrulline method, increased PGE content almost 100% as measured by RIA, and blocked stimulated salivary secretion. The administration of a specific iNOS inhibitor, aminoguanidine (AG), with LPS not only decreased NOS activity but significantly decreased PGE content, indicating that NO triggered the activation of COX-2. LPS increased conversion of labeled arachidonate to prostaglandins (PGs) showing that COX was induced. Since a PGE1 analogue blocked stimulated salivation, the LPS-induced inhibition of salivation is probably due to release of PGs. Therefore, the use of inhibitors of iNOS and COX-2 could be very useful to increase salivation during infection since saliva has antimicrobial actions.

Animals↗
PubMed2005

Advantages for transdermal over oral oxybutynin to treat overactive bladder: Muscarinic receptor binding, plasma drug concentration, and salivary secretion.

To clarify pharmacological usefulness of transdermal oxybutynin in the therapy of overactive bladder, we have characterized muscarinic receptor binding in rat tissues with measurement of plasma concentrations of oxybutynin and its metabolite N-desethyl-oxybutynin (DEOB) and salivation after transdermal oxybutynin compared with oral route. At 1 and 3 h after oral administration of oxybutynin, there was a significant increase in apparent dissociation constant (Kd) for specific [N-methyl-3H]scopolamine ([3H]NMS) binding in the rat bladder, submaxillary gland, heart, and colon compared with control values. Concomitantly, submaxillary gland and heart showed a significant decrease in maximal number of binding sites (Bmax) for [3H]NMS binding, which lasted until 24 h. Transdermal application of oxybutynin caused dose-dependent increases in Kd values for specific [3H]NMS binding in rat tissues. The increment of Kd values by transdermal oxybutynin was dependent on the application time. Plasma concentrations of oxybutynin and DEOB peaked at 1 h after oral oxybutynin. In contrast, plasma concentrations of oxybutynin increased slowly, depending on the transdermal application time of this drug until 12 h. Suppression of pilocarpine-induced salivation in rats due to transdermal oxybutynin was significantly weaker and more reversible than that by oral oxybutynin, which abolished salivary secretion. The present study has shown that transdermal oxybutynin binds significantly to rat bladder muscarinic receptors without producing both long-lasting occupation of exocrine receptors and cessation of cholinergic salivation evoked by oral oxybutynin. Thus, the present study provides further pharmacological basis for advantage of transdermal over oral oxybutynin in the therapy of overactive bladder.

Administration, Cutaneous↗
PubMed2001

Treatment of sialorrhoea with ultrasound guided botulinum toxin type A injection in patients with neurological disorders.

OBJECTIVES: To investigate the safety and efficacy of ultrasound guided botulinum toxin type A (BTX-A) injections into salivary glands for the treatment of sialorrhoea in patients with neurological disorders. METHODS: The parotid and submandibular glands of 10 patients were injected with BTX-A using ultrasound guidance. Before injection, the baseline rate of salivation was assessed using a visual analogue scale. Postinjection, assessments were repeated at regular intervals for up to 1 year. RESULTS: Of the 10 patients treated, nine (90%) reported a subjective reduction in salivation post-treatment and one patient (10%) found no improvement. Visual analogue scale scores showed a reduction of 55% in the mean rate of salivation for all patients and a reduction of 60.8% for the group of responders. No serious adverse events occurred and no procedure related complications were reported. CONCLUSIONS: This is the first study to report (1) the injection of BTX-A (BOTOX) into both parotid and submandibular glands, and (2) the use of ultrasound guidance during the administration of BTX-A into salivary glands. The results suggest that the technique is safe and that BTX-A injections are effective for the treatment of sialorrhoea in patients with neurological disorders.

Adult↗
PubMed2001

Inhibition of salivary secretion by lipopolysaccharide: possible role of prostaglandins.

Inducible (calcium-independent) nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are important in the regulation of the function of different organs during infection. A single dose of lipopolysaccharide (LPS; 5 mg/kg ip) within 6 h increased NOS activity (20%) and prostaglandin E (PGE) content (100%) in submandibular glands (SMG) and blocked stimulated salivary secretion in adult male rats. The administration of an iNOS synthesis inhibitor, aminoguanidine (AG), with LPS decreased NOS activity and PGE content. Furthermore, the administration of meloxicam (MLX), an inhibitor of COX-2, blocked the increase in PGE and the production of NO. The incubation of slices of SMG in the presence of 3-morpholinosydnonimine, a donor of NO, increased the release of PGE highly significantly. The incubation of SMG in the presence of a PGE(1) analog (alprostadil) increased the production of NO. These results indicate that LPS activates NOS, leading to NO release, which activates COX, generating PGEs that act back to further activate NOS, causing further generation of PGEs by activation of COX. Because the alprostadil administration inhibited stimulated salivation, LPS-induced inhibition of salivation appears to be caused by increased PGE production. Diminished salivary secretion produces poor oral health; thus the use of COX-2 inhibitors to counteract the effects of inhibited salivation should be considered.

Alprostadil↗
PubMed1987

Quantitation of phosphorus excretion in sheep by compartmental analysis.

The control of phosphorus excretion in sheep has been examined by constructing a kinetic model that contains a mechanistic set of connections between blood and gastrointestinal tract. The model was developed using experimental data from chaff-fed sheep and gives an accurate description of the absorption and excretion of phosphorus in feces and urine of the ruminating sheep. Simulation of the response to an intravenous phosphorus infusion by adding an inflow of 2 g/day of phosphorus into the compartment describing blood, predicted values for fecal output of phosphorus lower than found experimentally. However, by alteration of the parameters describing absorption or salivation, the predictions approached experimental values. Similarly simulation of the conditions existing when a liquid diet was infused directly into the abomasum, i.e., a decrease in salivation rate [L(4.1)] and dietary phosphorus entering compartment 5 (abomasum) instead of compartment 4 (rumen), gave incorrect predictions for plasma and urinary phosphorus, but when the parameter for urinary phosphorus was increased the predicted values approached experimental values. These results indicated the main control site for phosphorus excretion in the ruminating sheep was the gastrointestinal tract, whereas for the nonruminating sheep fed the liquid diet, control was exerted by the kidney. A critical factor in the induction of adaptation of phosphorus reabsorption by the kidney was the reduction in salivation, and since this response occurred independently of marked changes in the delivery of phosphorus to the kidney, a humoral factor may be involved in this communication between salivary gland and kidney.

Animals↗
PubMed1995

Salivary secretion in cat submandibular gland mediated by chorda tympani afferents.

The aim of the present study was to investigate whether the afferent traffic from the tongue mediated only via the chorda tympani nerve (CTN) can still elicit reflex salivary and vasodilator responses in the cat submandibular gland (SMG) after section of the lingual nerve proper (LNP). Electrical stimulation of the chorda lingual nerve (CLN) at a site approximately 5 mm distal to the intersection of the CLN and the SMG duct elicited salivary and vasodilator responses in the SMG in sympathectomized cats. Both responses were unaffected by section of the LNP. The optimal frequency of CLN stimulation for submandibular salivation and vasodilation was 20 Hz, regardless of whether the LNP had been cut. Prior treatment with the autonomic ganglion blocker hexamethonium (10 mg/kg iv) virtually abolished the salivation and the blood flow increase in SMG. Prior treatment with scopolamine (0.1 mg/kg iv) almost abolished the salivary secretions but had no effect on the vasodilator responses in the SMG elicited by CLN stimulation after LNP section. The mechanism underlying the reflex submandibular salivation mediated by chorda tympani afferents appears to involve parasympathetic muscarinic receptors, but the mechanism for the vasodilator response has yet to be established. These results indicate that afferent traffic passing through the CTN on CLN stimulation is importantly involved in the parasympathetic reflex secretory and vasodilator responses in the cat SMG.

Adrenergic Antagonists↗
PubMedDate not supplied

Role of nitric oxide in salivary secretion.

Since nitric oxide has been found to control the function of many organs of the body by the non-adrenergic, non-cholinergic branch of the autonomic nervous system, we hypothesized that it might play a role in salivary secretion. Therefore, we investigated the distribution of nitric oxide synthase (NOS) throughout the submaxillary gland and also studied the ability of inhibitors of NOS to interfere with salivation induced by a cholinergic agonist, metacholine, and by a polypeptide, substance P. The secretory responses were determined in rats anesthetized with chlorolose following intravenous injection of the various pharmacological agents. There was no basal flow of saliva and dose-response curves were obtained by sequential intravenous injection of increasing doses of the drugs. Then, in the same animal, the same dose-response curves were performed in the presence of NOS inhibitors. L-Nitro-arginine-methyl-ester (L-NAME; 20 mg/kg) produced an over 50% inhibition of the dose-related salivation induced by metacholine. Similar results were produced with L-NG-monomethyl-L-arginine (L-NMMA; 5 mg/kg). The salivation induced by much lower molar doses of substance P was dramatically greater than that obtained with metacholine. The response to substance P was almost completely inhibited by L-NMMA at the lowest dose (0.3 mg/kg), but at higher doses (1 mg/kg), the inhibition was only around 60% and at the highest dose (3 mg/kg) only about 20%. In control rats, there were roughly equal amounts of calcium-dependent and calcium-independent NOS in the gland at this time. At the end of the experiment, the effect of the inhibitor of NOS, L-NMMA, on the NOS activity in the submandibular gland was determined. At this time, the Ca2+-dependent NOS was decreased and the Ca2+-independent NO was increased. The prior injection of L-NMMA reduced calcium-dependent NOS activity by approximately 70% but calcium-independent activity by only 30%. These results indicate that, at least at the end of the experiment, the blockade of NOS imposed by NMMA was incomplete. This could account in part for the failure of the inhibitors to block completely the stimulatory effect of the two secretagogues. Analysis of the distribution of NOS in the salivary gland revealed that it was not present in the acinar cells, but in neural terminals within the gland and also in the ductile system which contained neural (n) NOS in the apical membrane of the excretory and striated ducts, the cytoplasm of granular convoluted tubules and, to a lesser extent, in the cytoplasm of excretory and striated ducts. Macrophage (inducible) NOS was also found not only in the macrophages, but also in the tubules and ducts. Since drugs were used that would act on the receptors in the gland, the role of NO in our conditions is probably mediated by nNOS and iNOS in the ductile and tubular structures. Since iNOS would already be active, it is unlikely to play a role in this acute secretory activity. Rather the nNOS in these non-neural cells is probably activated by muscarinic or K1 receptors by metacholine and substance P, respectively, leading to an increase in intracellular free calcium that activates NOS leading to the generation of cGMP that opens ion channels to initiate the secretory process.

Animals↗
PubMed1987

Transcapillary transport during secretion by the rabbit submandibular salivary gland.

Fluid exchange in the rabbit submandibular gland has been studied with a view to improving understanding of the mechanisms underlying transcapillary transport during salivation. Using maximally vasodilated glands perfused in vitro, we found that acetylcholine had no significant effect on either hydraulic conductance (filtration coefficient, Lp) or reflection coefficient to albumin (sigma alb) of the gland microvessels. In vivo, parasympathetic nerve stimulation increased blood flow 20-fold, interstitial fluid production (total fluid efflux - saliva flow) increased approximately 10-fold, while filtration fraction remained constant. At the same time, isogravimetric capillary pressure increased about six-fold. There are several possible explanations for these findings, and it is argued that they are likely to include capillary recruitment. Thus, during salivation, parasympathetic nerve stimulation does not lead to a change in capillary permeability as such, but rather produces a relaxation of resistance vessels and a fall in precapillary resistance, accompanied by an increase in available capillary surface area. This leads to a rise in capillary blood flow and pressure, which in turn increase fluid filtration. These changes are self-limiting due to the resulting dilution of interstitial protein and rise in interstitial pressure, but during salivation, since the secretion is pumped out of the interstitium, this fluid transport has no net effect on transcapillary gradients.

Acetylcholine↗
PubMed2000

Comparison of donepezil-, tacrine-, rivastigmine- and metrifonate-induced central and peripheral cholinergically mediated responses in the rat.

There are now several acetylcholinesterase inhibitors in clinical use for the treatment of Alzheimer's disease, however, no systematic comparative studies of their central and peripheral cholinergic mediated effects in rats appear to have been reported. The present study investigated the dose-response characteristics of donepezil, tacrine, rivastigmine and metrifonate in inducing tremor, lacrimation, salivation and hypothermia and the duration of action of these compounds in Lister hooded rats. Data obtained were compared with the clinical observations on these drugs. Three doses of each compound were given orally to establish a dose-response curve for each behaviour, Tremor and lacrimation were scored, salivation was measured by weighing swabs applied to the mouth area and hypothermia was measured with a rectal probe. ED50 values were calculated for tremor. Using a just sub-maximal tremorigenic dose, the duration of response was examined. All four compounds produced dose-dependent increases in tremor and hypothermia. Only tacrine also produced marked salivation and lacrimation. The order of potency (ED50 value in micromol/kg) was rivastigmine (3.7), donepezil (18.0), tacrine (37.5), metrifonate (470). Tremor following tacrine (150 micromol/kg) and donepezil (20 micromol/kg) was prolonged (> 6 h) with a similar hypothermic response. The duration of these responses following metrifonate (777 micromol/kg) and rivastigmine (12.5 micromol/kg) did not exceed 3 h. Tacrine had poor selectivity for central (tremor) versus peripheral (salivation/lacrimation) effects compared to the other compounds. Donepezil also had a sustained duration of action. The data are consistent with clinical results and indicate that simple in-vivo models may assist in the selection of acetylcholinesterase inhibitors with a suitable response profile for use in the symptomatic treatment of Alzheimer's disease.

Animals↗
PubMed1990

Inter-organ relation between salivary gland and kidney in lithium excretion. III. Enhanced salivary and systemic clearance of Li+ by oral administration of NaCl in dogs.

Effects of oral administration of NaCl on salivary and systemic clearance of Li+ were investigated following bolus intravenous administration of LiCl in male beagle dogs. Fifty ml of NaCl solution (100 meq/l) was administered orally 7 times at 1 h intervals. Gustatory stimulation of salivation was continued for 390 min using citric acid solution. Saliva was collected by means of permanent fistulae for parotid and mandibular-sublingual glands. Salivary clearance of Li+ was markedly increased by continuous stimulation of salivation, and was enhanced further after oral administration of NaCl solution. Renal clearance of Li+ showed a decreasing tendency under continuous salivation compared with the condition without gustatory stimulation; however, this decreasing tendency disappeared after oral administration of NaCl solution. Consequently, systemic clearance of Li+ was increased due to the contribution of increased salivary clearance. Enhancement of salivary Li+ clearance after administration of NaCl suggests the salivary excretion mechanism of Li+ may include a reabsorption process, like its renal excretion. Administration of NaCl solution had similar effects on salivary and systemic clearances of K+ to those on Li+ clearances, and a significant correlation was observed between Li+ and K+ clearances of both salivary gland and kidney.

Animals↗
PubMed1989

Effects of metaraminol on the secretion of fluid and glycoproteins from the rat submandibular gland.

The actions of metaraminol on the secretion of fluid and glycoproteins from rat submandibular glands were investigated using phentolamine, propranolol and reserpine. Metaraminol at doses from 1 to 8 mg/kg (i.p.) increased the salivation and the amounts of protein in submandibular saliva in a dose-dependent manner. The salivation induced by metaraminol at 2 mg/kg was inhibited strongly by pretreatment with propranolol, whereas the salivation induced by metaraminol at 8 mg/kg was inhibited strongly by phentolamine. Reserpine inhibited the secretion of fluid caused by both doses of metaraminol. The electrophoretic profiles of saliva evoked by metaraminol at 2 mg/kg revealed two main bands of glycoprotein, I and IV, which originated from the acinus, and the intensities of these bands were decreased by treatment with propranolol, whereas the major band in saliva induced by 8 mg/kg of metaraminol was glycoprotein III, which originated from the granular tubules. The intensity of band III was decreased by pretreatment with phentolamine. These results suggest that metaraminol, at small doses, stimulates mainly the beta-adrenoceptor in the acinus, whereas at large doses, it prominently stimulates the alpha-adrenoceptors in the granular tubules, although metaraminol at small and large doses is able to stimulate alpha- and beta-adrenoceptors in rat submandibular gland.

Animals↗
PubMed1993

Alcohol cue reactivity: effects of detoxification and extended exposure.

Alcoholics' reactions to drinking-related stimuli (cue reactivity) have been well documented and alcohol cue exposure treatment has been conducted recently in several clinical trials. Prior to conducting large-scale clinical trials it is important to know what effects detoxification may have on cue reactivity. However, no information is available about the effects of stage of detoxification or of detoxification medication on alcohol cue reactivity. In this study, 45 male alcoholics, detoxified without medication, were assessed during either their second, fourth or sixth day of withdrawal. Further, their reactivity was compared to that of alcoholics detoxified with chlordiazepoxide (n = 15), and to that of alcoholics in their fourth week after drinking (n = 28). Cue reactivity assessment investigated salivation and urge to drink after 3 minutes of water cue exposure and then after 3 minutes of alcohol cue exposure. Urges to drink were assessed during an additional 15 minutes of alcohol exposure to explore latency to maximum reactivity and habituation. Reactivity did not differ as a function of group membership, although salivation was elevated to both beverages during the first week of detoxification. Of the sample, 70% reacted to alcohol with increased urge and 65% with increased salivation, with no difference between groups in proportions of reactors. The maximum urge to drink occurred in the first 6 minutes of alcohol exposure, followed by a gradual and significant decrease. There were no differences on these measures between alcoholics in their first or fourth week after their last drink. Implications for theory and clinical applications are discussed.

Adaptation, Psychological↗
PubMed2004

Use of neostigmine in massive ivermectin toxicity in cats.

Over-the-counter availability of drugs in developing countries poses the risk of their abuse and overdosing in animals by the owners. This report describes ivermectin toxicosis and its treatment with neostigmine methylsulfate in 2 kittens and an adult cat that had been massively overdosed by their owners. Of two 4-w-old 300 g kittens, one was injected with 1.5 ml ivermectin (15 mg; corresponding to 250 times the recommended dose) by the owner and became comatose, started salivation and died after 2 1/2 h. The other kitten was treated with about 0.75 ml ivermectin (7.5 mg; corresponding to 125 times the recommended dose) by the same owner and developed ataxia and salivation after 2 h, went into coma the next morning and was presented for treatment with mydriasis, coma, slight fever (102.4 F), tachypnea (48/min) and severe tachycardia. This kitten was treated twice at a half hourly interval with neostigmine methylsulfate (25 microg) and 5% dextrose (20 ml) iv showed a transient improvement but died 12 h later. A 2-y-old, 4.5 kg male cat was treated s.c. with 1.5 ml ivermectin (15 mg; corresponding to 16.6 times the recommended dose) by its owner and developed slight salivation, lacrimation. mydriasis, protrusion of third eye-lid, tachypnea (42 breaths/min), tachycardia (128 beats/min) and ataxia. The patient was treated with neostigmine methylsulfate (150 microg) and 5% dextrose (100 ml) i.v., and 200 ml of Heartmann's solution i.v. Treatment was repeated after 6 h Follow up treatment over next 2 d was with daily i.v. administration of neostigmine and dextrose. The patient completely recovered 5 d after initiation of treatment.

Animals↗
PubMed1991

[Oral lesions in a group of heroin addicts].

Lesions of the oral mucous membrane are studied in 100 heroin dependent people compared with 100 control, other habits like smoking, alcohol ingesting and sexual oral practices are also taking in consideration. Salival flux and other salival characteristics are also analyzed. The heroin dependent people show significative increase in salival filament but this difference that's not exit of we also analyze in the lesions of lips, tongue, palate and vestibule in relation to controls. Nevertheless in the take into account only smokers and drinkers of both groups the only lesions significantly more frequent are those on the lips.

Adult↗
PubMed1986

Pharmacological properties of the novel antimuscarinic agent 4-[2-(1,2-benzisoxazol-3-yl)-2-(hexahydro-1H-azepin-1-yl)a cetoxy]-1-et hyl-1- methylpiperidinium iodide.

Pharmacological properties of 4-[2-(1, 2-benzisoxazol-3-yl)-2-(hexahydro-1H-azepin-1-yl)acetoxy]-1- ethyl-1- methylpiperidinium iodide (SX-810) were investigated and the following results were obtained. 1. In isolated guinea-pig ileum, SX-810 showed a competitive antagonistic effect against acetylcholine with a pA2 value of 7.93. 2. SX-810 (10-50 mg/kg p.o. or 10-50 micrograms/kg i.v.) inhibited the gastroduodenal contractions induced by bethanechol and carbachol in anaesthetized rats. 3. SX-810 (10-100 mg/kg p.o.) inhibited spontaneous gastric motility in conscious rats and rabbits. 4. SX-810 (10-100 mg/kg p.o.) inhibited gastric secretion in pylorus-ligated rats. 5. SX-810 (20-200 mg/kg p.o. or 1-10 mg/kg s.c.) inhibited the ulceration induced by pylorus ligation or by exposure to restrained and water-immersed stress in rats. 6. When administered orally to rats, SX-810 had no mydriatic effect even at 3000 mg/kg, but subcutaneously administered SX-810 (0.5-10 mg/kg) exhibited such action. 7. When administered orally to rats, SX-810 (100-500 mg/kg) caused no significant inhibition of the salivation induced by pilocarpine, but subcutaneously administered SX-810 (0.5-10 mg/kg) exhibited an inhibition of the salivation. In rabbits, SX-810 (200-500 mg/kg p.o.) also caused no significant inhibition of the salivation except at an extremely high dose of 1000 mg/kg p.o. 8. SX-810 (100-500 mg/kg p.o.) caused no significant effect on urine and electrolyte excretion in rats. These results indicate that oral use of SX-810 exhibits marked spasmolytic and antiulcerative activities without exerting systemic antimuscarinic side effects.

Animals↗