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PubMed2001

The impact of familial alcoholism on alcohol reactivity in female social drinkers.

Some individuals may have an inherent reactivity to alcohol that facilitates early development of characteristics associated with alcoholism. Although response to alcohol cues has been used to assess this reactivity, few studies have included women or investigated familial alcoholism as a variable. In this study, 23 female college students were divided into groups according to family history of alcoholism (positive or negative). Alcohol reactivity was measured by salivation, skin temperature, heart rate, mood state, and craving for alcohol following presentation of alcohol-related and neutral cues. Results indicate no correlation between salivary reactivity and alcohol craving, which suggests that these variables tap into different domains of cue reactivity. Findings demonstrate that alcohol cue reactivity can be assessed in female social drinkers and that familial alcoholism may influence salivary reactivity to alcohol-related cues.

Adult↗

PubMed1983

Chronopharmacology of amitriptyline.

Side effects of decreased salivation and sedation were more marked when a single dose of amitriptyline was taken orally in the morning than in the evening. These dynamic differences were due to alteration in kinetics. Absorption of the drug was more rapid in the morning, although other kinetic parameters, especially total bioavailability, were unchanged. Thus, in the case of this drug, chronopharmacologic differences were due to a change in rate of absorption. The present practice of giving a single dose of drug in the evening is justified on the basis that it induces fewer side effects without a loss in therapeutic efficacy.

Absorption↗

PubMed1993

Is salivary flow related to personality?

Studies conducted in the 1960s proposed that stimulated salivary flow was negatively correlated with the personality trait of introversion-extraversion such that introverted individuals were supposed to salivate more strongly to lemon-juice stimulation than were extraverts. The relationship was re-examined in the present study in light of more recent but inconsistent findings. A sample of 36 male and female volunteers showed no significant relationship between stimulated salivary flow and extraversion. Nor was flow related to State or Trait anxiety according to Spielberger's anxiety inventory, or to CNS activation as assessed by an objective electronic test. It was concluded that there was no evidence to relate stimulated salivary flow rates to personality in volunteers selected from a non-psychiatric population.

Adult↗

PubMed2003

Effects of nicotine deprivation on urges to drink and smoke in alcoholic smokers.

AIM: This study examined the effect of nicotine deprivation on alcohol and smoking urges in a sample of alcohol-dependent smokers in early recovery. DESIGN: Using a within-subjects design, participants underwent two cue-reactivity laboratory sessions in which they rated their urges for alcohol and cigarettes during the following three trials: baseline, neutral cue and mood induction combined with alcohol beverage cue exposure. One session was completed after 34 hours of nicotine deprivation and another in a non-deprived state. PARTICIPANTS: Forty alcohol-dependent heavy smokers recruited from a substance abuse day treatment program. MEASUREMENTS: Self-reported urge to drink, urge to smoke and salivation. FINDINGS: Results showed that during the non-deprived session, alcohol cue presentations were associated with significant increases in urges to drink and urges to smoke. Acute nicotine deprivation led to increased smoking urges, but was not associated with increased urges to drink alcohol. CONCLUSIONS: Findings suggest that the acute effects of smoking cessation are unlikely to increase risk of relapse to alcohol in alcoholic patients who are undergoing treatment.

Adult↗

PubMed2002

Nizatidine and cisapride enhance salivary secretion in humans.

BACKGROUND: Salivation plays an important role in the defence of the oesophageal mucosa against gastric acidic reflux and can be evoked by cholinergic stimulation. Both nizatidine and cisapride have been reported to increase acetylcholine concentrations in the cholinergic system. AIM: To investigate the effect of nizatidine and cisapride on salivary secretion, salivary epidermal growth factor and bicarbonate output. METHODS: The salivary volume and concentration of salivary epidermal growth factor and bicarbonate were measured after the administration of nizatidine (150 mg), famotidine (20 mg) and cisapride (5 mg) in 30 male healthy volunteers. RESULTS: Basal and stimulated salivary secretions were found to be increased after the administration of nizatidine and cisapride. In contrast, salivary secretion was not increased by famotidine. Although epidermal growth factor content was not augmented, nizatidine and cisapride administration also increased the bicarbonate output in mastication-stimulated saliva. CONCLUSIONS: Increased salivary secretion and bicarbonate output induced by nizatidine may be useful for the treatment of patients with gastro-oesophageal reflux disease.

Adult↗

PubMed2003

The cause of drooling in children with cerebral palsy -- hypersalivation or swallowing defect?

OBJECTIVE: To determine whether or not drooling in children with cerebral palsy is due to hypersalivation. POPULATION AND METHODS: The study population consisted of 10 children with cerebral palsy who were identified as having severe drooling, and a matched control group composed of 10 unaffected children who had no known physical or mental disabilities. Salivary flow rate was compared between the cerebral palsied children and the control group using the chin-cup collection drool quantification method described by Sochanjwskyj. Components of the system included a cup-like collection device, a vacuum pump, plastic tubing, an airtight collection chamber, and calibrated test tubes held against the subject's chin with elastic straps attached to an orthodontic head bonnet. Statistical analysis was completed using the Student's t-test and Fisher's Exact Probability test. RESULTS: The ages of the population ranged from 5.2 to 15.6 years, mean age (+/- SE) of 10.56 +/- 1.13 years. There was no statistically significant difference in the rate of salivary flow rate between the two groups' mean +/- SE: cerebral palsy group 0.220 +/- 0.018; control group 0.334 +/- 0.052 (P = 0.053). The results were further confirmed by comparing the buffering capacity (P = 1.00) and concentrations of the sodium (P = 0.065) and potassium ions (P = 0.058) in the saliva of the study groups. CONCLUSIONS: Children with cerebral palsy who drool do not appear to produce excess saliva. Their salivation is similar to the control children.

Adolescent↗

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↗

PubMed1997

Plasma concentration following oral and intramuscular atropine in children and their clinical effects.

In a paediatric population, we compared i.m. v oral atropine premedication to a control group without atropine and determined atropine plasma concentrations (APC). Forty-five children were randomly assigned to one of three groups. Group I received atropine, 20 micrograms.kg-1 i.m., 15 min prior to induction. Group II received atropine, 30 micrograms.kg-1 orally, group III received no atropine. APC (expressed as percent of muscarine-2 receptor subtype occupancy), heart rate, rectal temperature, and salivation were determined before atropine, and 15, 25, 45, 60, 90, 120 (no APC), and 150 min following atropine. Only 10-20% of the M2-cholinoceptors were occupied after oral atropine with a peak at 90 min compared to 60-70% occupancy with a peak 25 min after i.m. atropine. The peak in M2-cholinoceptor occupation in group I was paralleled by a peak percentage change in heart rate of 15% from baseline. The peak in receptor occupation in group II did not correspond to the peak increase in heart rate. The percentage change of heart rate over time was not significantly different from baseline values in any of the groups. Bradycardia or temperature changes did not occur in any of the groups. Antisialogogue effects were observed only in group I. We conclude that atropine; 30 micrograms.kg-1 orally is not an equipotent dosage to atropine, 20 micrograms.kg-1 i.m.

Administration, Oral↗

PubMed2001

Systemic effects of intravesical atropine sulphate.

OBJECTIVE: To investigate systemic antimuscarinic activity after the intravesical administration of 6 mg of atropine sulphate. SUBJECTS AND METHODS: Ten subjects were recruited to an open study in accordance with strict inclusion and exclusion criteria. Each subject received an instillation of 6 mg atropine sulphate diluted to 20 mL with normal saline. All variables were measured at baseline (before instillation) and the instilled solution retained for at least 2 h. After instillation systemic antimuscarinic activity was monitored every 20 min for 2 h then hourly for the next 4 h. The measurements included blood pressure, sublingual temperature, pulse rate, peak expiratory flow rate, lacrimation and salivation rates; all variables were analysed statistically. Facial skin was also observed for hyperaemia. All subjects were questioned about any known symptoms produced by antimuscarinic agents. The heart rate was recorded continuously before and after instillation using a Holter monitor. RESULTS: None of the variables changed significantly after instillation and the Holter analysis showed no relevant variation in heart rate. All subjects consistently denied any antimuscarinic symptoms. One subject had mild cutaneous hyperaemia, as reportedly occurred consistently when her bladder was distended (> 500 mL). Immediate catheterization drained 600 mL and the hyperaemia resolved. CONCLUSION: The failure to detect systemic antimuscarinic activity at a dose which has previously been shown to suppress detrusor activity suggests that intravesical atropine therapy is safe for further study by clinical trial, and might provide a treatment for detrusor hyper-reflexia that is free from side-effects.

Administration, Intravesical↗

PubMed2003

Up-to-date report of botulinum toxin therapy in patients with drooling caused by different etiologies.

PURPOSE: In this study, we evaluated the clinical data for patients with drooling caused by various diseases, treated by injection of botulinum toxin A. We also present a controlled follow-up study documenting efficiency, possible adverse events, and duration of the effect of treatment. PATIENTS AND METHODS: Thirteen patients with drooling caused by head and neck carcinoma, neurodegenerative diseases, or stroke received injections of 50 to 65 U botulinum toxin A (Botox; Allergan, Irvine, CA) in both submandibular and both parotid glands under sonographic control. We measured whole salivary flow rate and the salivary analytes of total protein, alpha-amylase, acid phosphatase, kallikrein, and immunoglobulin A at various times before and after injection. The patients were examined for severity of symptoms, including sonographic investigation of cephalic salivary glands. RESULTS: All 13 patients reported a distinct improvement of their symptoms within 2 weeks after toxin injection. Three patients noted a return of high salivation rates after 12 weeks. Duration of toxin effect varied widely between individuals. In general, salivary flow rates dropped sharply within 1 week after injection but had risen again after 12 weeks. Conversely, analyte concentrations increased in the first stages of treatment and later decreased, returning to pretherapy levels. Sonography did not reveal any major changes of salivary gland parenchyma, and side effects were absent. CONCLUSIONS: Local injection of botulinum toxin A into the salivary glands proved to be a dependable therapy for drooling caused by various etiologies, as shown in 13 patients. Adverse events were not seen. The effect of toxin application lasted for about 3 months. To further clarify this aspect, long-term studies are under way.

Adolescent↗

PubMed1988

Absence of anticholinergic activity of rolipram, an antidepressant with a novel mechanism of action, in three different animal models in vivo.

Rolipram, in contrast to the tricyclic antidepressants amitriptyline and imipramine or the acetylcholine receptor antagonist atropine, failed to antagonize the salivation, hypothermia, or tremor caused in mice by the muscarinic receptor agonists pilocarpine or oxotremorine. The absence of anticholinergic activity, the extremely low therapeutic dose, and the novel mechanism of antidepressant action suggest that rolipram may also be a well tolerable antidepressant suitable for the treatment of problematic subpopulations of depressives such as elderly patients.

Animals↗

PubMed2001

The influence of pilocarpine and biperiden on pH value and calcium, phosphate, and bicarbonate concentrations in saliva during and after radiotherapy for head and neck cancer.

OBJECTIVE: The purpose of the present study was to investigate the influence of parasympathomimetic pilocarpine and anticholinergic biperiden on salivation, pH value, and calcium, phosphate, and bicarbonate concentrations in saliva in patients irradiated for malignant tumors of the head and neck region. STUDY DESIGN: Sixty-nine patients were randomly assigned into 3 groups. Group A consisted of patients receiving pilocarpine, group B of those who were receiving biperiden during radiotherapy and pilocarpine for 6 weeks after its completion, and group C comprised patients receiving neither of the mentioned drugs. The quantity of secreted unstimulated saliva, its pH value, as well as calcium, phosphate, and bicarbonate concentrations in saliva were measured before the beginning of radiotherapy, after 30 Gy of irradiation, at completed irradiation, and 3, 6, and 12 months after completion of radiotherapy. RESULTS: Saliva secretion was found to be the least affected in the group of patients receiving biperiden throughout the course of radiotherapy. One year after completion of therapy, the quantity of secreted saliva could only be measured in the patients receiving biperiden during radiotherapy; it amounted to 16% of the average initial quantity of saliva secreted before the beginning of irradiation. In all 3 groups of patients, mean pH value decreased during radiotherapy and started to increase again after completion of irradiation. In group B the decrease in pH value after radiotherapy was statistically significantly smaller than that in group C (P =.01). During and after irradiation, calcium concentration was increased in all 3 groups of patients. Phosphate concentration decreased during radiotherapy in all 3 groups. In group B it started to increase again 3 months after completion of radiotherapy. Bicarbonate concentration showed a slight increase during radiotherapy and started to decrease again after completion of irradiation. CONCLUSION: The results of our study indicate that the inhibition of saliva secretion during radiotherapy and its stimulation after completion of treatment can contribute not only to some preservation of the quantity of saliva but also to at least partial preservation of its quality in terms of pH value and calcium, phosphate, and bicarbonate concentrations.

Administration, Oral↗

PubMed1976

alpha-Adrenergic regulation of secretion of mouse saliva rich in nerve growth factor.

Nerve growth factor has been quantified by both bioassay and radial immunodiffusion in mouse saliva elicited by several secretagogues. The concentrations by bioassay of nerve growth factor in both epinephrine- and norepinephrine-induced saliva (3400 and 900 mug/ml, respectively) are higher than reported in any other source. In contrast, the concentrations of nerve growth factor in isoproterenol- and pilocarpine-induced saliva are relatively low (17 and 2 mug/ml, respectively). The specific activity of the salivary nerve growth factor was 41, 36, 2, and 0.6 mug/mg of protein in secretions elicited by epinephrine, norepinephrine, pilocarpine, and isoproterenol, respectively. Salivation after administration of either epinephrine or norepinephrine was completely inhibited by the alpha-adrenergic blocker, phenoxybenzamine. These results suggest that the release of saliva rich in nerve growth factor is primarily regulated through alpha-adrenergic receptors.

Animals↗

PubMed1978

Endorphins may function in heat adaptation.

Administration of the opiate antagonist naloxone to rats after acute or chronic heat exposure precipitates an increase in colonic temperature, an increase in escape attempts, and a decrease in body weight. These changes are accompanied by signs associated with hyperthermia such as salivation, diarrhea, and an abnormal extended posture. Although brain endorphin involvement is possible, hypophysectomy diminishes the intensity and magnitude of these naloxone effects, indicating that the naloxone effect in intact animals may be due to a functional antagonism of pituitary endorphins. These observations suggest that endorphins attenuate physiological responses to thermal and noxious stimuli triggered in common neuroanatomical pathways by heat.

Adaptation, Physiological↗

PubMed1999

Enhancement of D1 dopamine receptor-mediated locomotor stimulation in M(4) muscarinic acetylcholine receptor knockout mice.

Muscarinic acetylcholine receptors (M(1)-M(5)) regulate many key functions of the central and peripheral nervous system. Primarily because of the lack of receptor subtype-selective ligands, the precise physiological roles of the individual muscarinic receptor subtypes remain to be elucidated. Interestingly, the M(4) receptor subtype is expressed abundantly in the striatum and various other forebrain regions. To study its potential role in the regulation of locomotor activity and other central functions, we used gene-targeting technology to create mice that lack functional M(4) receptors. Pharmacologic analysis of M(4) receptor-deficient mice indicated that M(4) receptors are not required for muscarinic receptor-mediated analgesia, tremor, hypothermia, and salivation. Strikingly, M(4) receptor-deficient mice showed an increase in basal locomotor activity and greatly enhanced locomotor responses (as compared with their wild-type littermates) after activation of D1 dopamine receptors. These results indicate that M(4) receptors exert inhibitory control on D1 receptor-mediated locomotor stimulation, probably at the level of striatal projection neurons where the two receptors are coexpressed at high levels. Our findings offer new perspectives for the treatment of Parkinson's disease and other movement disorders that are characterized by an imbalance between muscarinic cholinergic and dopaminergic neurotransmission.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed2003

Oesophageal intraluminal nitric oxide facilitates the acid-induced oesophago-salivary reflex.

BACKGROUND: The present study explores some aspects of the triggering of the acid-induced oesophago-salivary reflex. In addition to hydrogen ions, there are two acid-dependent molecules with messenger potential in the oesophageal lumen: CO2 and NO. The aim of this study was to clarify whether oesophageal NO and CO2 participate in the regulation of salivary neutralizing capacity in response to acid exposure. METHODS: Healthy volunteers received oesophageal acidification composed of HCl, with NO3-, or HCO3- or NO3- and HCO3- in combination. In a second series of experiments, the exposure period was divided into 2 separate 10-min events. Saliva volume and titratable buffering capacity were used to calculate alkaline secretion. RESULTS: Salivary alkaline secretion increased markedly following 20 min intraluminal exposure to HCl. The initial part of this response was 22% +/- 2.2% larger (P < 0.05) if NO3- was present. When HCO3- was added, or if NO3- and HCO3- were given simultaneously, the secretory response tended to be lower. The accumulated responses over 70 min to 2 short HCl exposures (10 min each separated by a 30 min 'rest') compared to one long one lasting 20 min were similar regardless of the presence of NO3-. CONCLUSION: The data suggest that oesophageal intraluminal NO facilitates initiation of the oesophago-salivary reflex. CO2 seems to have a negligible effect on alkaline salivation, and repeated stimulation does not influence the magnitude of the response over time.

Adult↗

PubMed1989

Clinical signs and biochemical changes in calves caused by injection of ivermectin.

Eight-month-old Jersey bull calves given ivermectin intravenously or subcutaneously showed signs of depression, ataxia, difficulty in breathing, tachycardia, salivation, diarrhoea, miosis, and an increase in pseudocholinesterase activity. The clinical signs were severe in calves given the drug intravenously. The findings suggest that the cholinergic nervous system may be involved in some of the adverse effects of ivermectin observed in calves.

Animals↗

PubMedDate not supplied

Lack of oncogenicity of wood creosote, the principal active ingredient of Seirogan, an herbal antidiarrheal medication, in Sprague-Dawley rats.

Seirogan, an herbal medicine containing wood creosote (tablets, 10.0% w/w), has been developed and marketed for almost a century in various countries for the control of acute diarrhea and treatment of associated symptoms, such as abdominal cramping. Wood creosote (CAS no. 8021-39-4) is a mixture of simple phenolic compounds, including guaiacol and creosol and related compounds, and is chemically distinct from, and should not be confused with, coal tar creosote, a known carcinogen. In the current study, the oncogenic potential of wood creosote was assessed in a 96/103-week oral gavage study in Sprague-Dawley rats. Groups of 60 rats/sex received wood creosote at dose levels of 20, 50, or 200 mg/kg body weight [bw]/day. An additional group of rats received the vehicle, 0.5% carboxymethylcellulose in deionized, distilled water, at the same dose volume as the treatment groups (10 ml/kg) and served as the controls. Treatment-related decreases in survival, body weight, and food consumption, as well as increased incidences of clinical signs that included rales, decreased activity, and salivation, were noted at 200 mg/kg bw/day when compared with the control group. There was an increased incidence of reddened and edematous lungs in rats from the 200 mg/kg bw/day group that died during the study. The lung findings were suggestive of test article aspiration during dose administration or agonal aspiration preceding and possibly resulting in death, especially because these observations were not seen in animals that survived to scheduled sacrifice. Additionally, phenols are generally recognized as having corrosive properties. There were no changes in clinical pathology and no increases in neoplastic or non-neoplastic lesions, excluding the lung findings, related to treatment with wood creosote at any dose level. Although the results of this study indicate that the maximum tolerated dose of wood creosote was met or exceeded at 200 mg/kg bw/day, there was no evidence of oncogenicity at any dose level. The lack of any evidence of oncogenicity supports the safety profile of the active ingredient in Seirogan, wood creosote.

Animals↗