piperidines and Xerostomia

Burning mouth syndrome (BMS) refers to chronic orofacial pain, unaccompanied by mucosal lesions or other evident clinical signs. It is observed principally in middle-aged patients and postmenopausal women. BMS is characterized by an intense burning or stinging sensation, typically on the tongue or in other areas of the oral mucosa. It can be accompanied by other sensory disorders such as dry mouth or taste alterations. Probably of multifactorial origin, and often idiopathic, with a still unknown etiopathogenesis in which local, systemic and psychological factors are implicated. Currently there is no consensus on the diagnosis and classification of BMS. This study reviews the literature on this syndrome, with special reference to the etiological factors that may be involved and the clinical aspects they present. The diagnostic criteria that should be followed and the therapeutic management are discussed with reference to the most recent studies.

Topics: Acetamides; Amines; Anti-Anxiety Agents; Antidepressive Agents; Antioxidants; Burning Mouth Syndrome; Chlordiazepoxide; Clonazepam; Cognitive Behavioral Therapy; Cyclohexanecarboxylic Acids; Female; Gabapentin; gamma-Aminobutyric Acid; Histamine H2 Antagonists; Humans; Male; Paresthesia; Peripheral Nervous System Diseases; Phantom Limb; Piperidines; Prognosis; Pyridines; Sex Factors; Thioctic Acid; Tongue; Xerostomia

Donepezil is an acetylcholinesterase inhibitor marketed for treatment of memory loss and behavioral deterioration associated with the acetylcholine deficit of Alzheimer's disease. We investigated the utility and tolerability of donepezil in nongeriatric affective illness for treatment of psychotropic-induced memory loss, dry mouth, and constipation.. Nondemented outpatients with stabilized DSM-IV affective illness took 5 mg/day of donepezil for 3 weeks and then increased to 10 mg/day in open trials. Self-rating scales of target symptoms were completed by patients before and 3 to 4 weeks after starting each dose condition. Patients who chose to continue donepezil therapy returned for clinical monitoring every 4 to 8 weeks.. Eleven women and 11 men (mean +/- SD age = 45.4+/-8.5 years) completed donepezil trials. Nineteen patients with memory loss rated improvement while taking 5 mg/day of donepezil (p<.001); subsequently, 6 rated further improvement with 10 mg/day (p = .057). Donepezil, 5 mg/day, also reduced ratings of dry mouth (N = 16; p<.001) and constipation (N = 11; p<.05). Side effects included insomnia, nausea, vomiting, and diarrhea; surprisingly, 2 bipolar patients became manic within hours of starting donepezil. Sixteen patients (72%) continued donepezil for an average of 7 months. Consideration of family histories suggested that donepezil response in affective illness may be an early indicator of vulnerability to dementia of the Alzheimer's type.. (1) Donepezil can reduce memory loss, dry mouth, and constipation in nongeriatric affective patients, but may trigger mania; and (2) long-term follow-up will reveal the predictive value for dementia of donepezil's memory restoration in nongeriatric subjects.

Topics: Adult; Ambulatory Care; Cholinesterase Inhibitors; Constipation; Depressive Disorder; Diarrhea; Dizziness; Donepezil; Drug Administration Schedule; Female; Humans; Indans; Male; Memory Disorders; Middle Aged; Piperidines; Psychotropic Drugs; Sleep Initiation and Maintenance Disorders; Xerostomia

Topics: Adolescent; Adult; Clinical Trials as Topic; Delayed-Action Preparations; Drug Evaluation; Fatigue; Female; Fluorobenzenes; Fluphenazine; Humans; Male; Middle Aged; Movement Disorders; Piperidines; Schizophrenia; Spiro Compounds; Tranquilizing Agents; Xerostomia

The second-generation antihistamines at licensed doses are first-line treatment in urticaria and up-dosing is recommended as second-line treatment. To assess the efficacy and safety of escalated doses of ebastine in patients with chronic urticaria (CU), we designed this study. Recruited patients with CU were treated with increasing doses of ebstine. Treatment started at the daily dose of 10 mg. The symptom is assessed weekly, and if there is no significant improvement, the dose is increased from 10 mg to 20 mg, and if still no significant improvement, up to 40 mg. Pruritus, number, diameter, duration and frequency of wheals, and adverse reactions were assessed. One hundred and forty (76.50%) patients achieved marked effect with ebastine 10 mg/day, 27 (14.75%) patients with ebastine 20 mg/day and 13 (7.10%) patients with ebastine 40 mg/day, while 3(1.64%) patients did not get marked effect. There was no significant difference of effect between factitious urticaria, CSU, cholinergic urticaria and CSU with factitious urticaria in different dose (all p > 0.05). Common adverse reactions of ebstine treatment, included dry mouth, somnolence, tiredness and headache, were mild or moderate. There was no significant difference between the degree score of dry mouth with different doses of ebastine, and the same to somnolence, tiredness and headache (all p > 0.05). Doses escalation of ebastine should be effective in treatment of factitious urticaria, CSU and cholinergic urticaria with poorly treated by standard of double doses. Increasing ebastine dose did not increase the incidence of adverse reactions.

Topics: Butyrophenones; Cholinergic Agents; Chronic Disease; Chronic Urticaria; Headache; Histamine H1 Antagonists; Humans; Piperidines; Prospective Studies; Sleepiness; Urticaria; Xerostomia

The aim of this study was to investigate the factors that could participate on salivary glands hypofunction during inflammation and the participation of endocannabinoids in hyposalivation induced by the presence of inflammogens in the submandibular gland (SMG) or in the brain.. Salivary secretion was assessed in the presence of inflammogens and/or the cannabinoid receptor antagonist AM251 in the SMG or in the brain of rats. At the end of the experiments, some systemic and glandular inflammatory markers were measured and histopathological analysis was performed.. The inhibitory effect observed 1h after lipopolysaccharide (LPS, 50μg/50μl) injection into the SMG (ig) was completely prevented by the injection of AM251 (5μg/50μl) by the same route (P<0.05). The LPS (ig)-induced increase in PGE2 content was not altered by AM251 (ig), while the glandular production of TNFα induced by the endotoxin (P<0.001) was partially blocked by it. Also, LPS injection produced no significant changes in the wet weight of the SMG neither damage to lipid membranes of its cells, nor significant microscopic changes in them, after hispopathological analysis, compared to controls. Finally, TNFα (100ng/5μl) injected intracerebro-ventricularly (icv) inhibited methacholine-induced salivary secretion evaluated 30min after (P<0.01), but the previous injection of AM251 (500ng/5μl, icv) prevented completely that effect.. We conclude that endocannabinoids mediate the hyposialia induced by inflammogens in the SMG and in the brain. The hypofunction would be due to changes on signalling pathway produced by inflammatory compounds since anatomical changes were not observed.

Topics: Analysis of Variance; Animals; Cannabinoid Receptor Agonists; Dinoprostone; Endocannabinoids; Hypothalamus; Inflammation; Lipopolysaccharides; Male; Piperidines; Pyrazoles; Radioimmunoassay; Rats; Rats, Wistar; Submandibular Gland; Thiobarbituric Acid Reactive Substances; Tumor Necrosis Factor-alpha; Xerostomia

We demonstrate that patients with primary Sjögren's syndrome (pSS) produce functional IgG autoantibodies that interact with the glandular M(3) muscarinic acetylcholine receptors (mAChRs). These autoantibodies act as a partial muscarinic agonist, increasing prostaglandin E(2) (PGE(2)) and cyclic AMP production through modifying Na(+)/K(+)-ATPase activity, but also interfere with the secretory effect of the parasympathetic neurotransmitter. The IgG from patients with pSS has two effects on the submandibular gland. On the one hand, it may act as an inducer of the proinflammatory molecule (PGE(2)) that, in turn, inhibits Na(+)/K(+)-ATPase activity. On the other hand, it plays a role in the pathogenesis of dry mouth, abolishing the Na(+)/K(+)-ATPase inhibition and the net K(+) efflux stimulation of the salivary gland in response to the authentic agonist pilocarpine, decreasing salivary fluid production.

Topics: Adult; Animals; Autoantibodies; Cells, Cultured; Cyclic AMP; Dinoprostone; Female; Humans; Immunoglobulin G; Immunologic Factors; Inflammation Mediators; Keratoconjunctivitis Sicca; Male; Middle Aged; Muscarinic Agonists; Muscarinic Antagonists; Pilocarpine; Piperidines; Pirenzepine; Potassium; Rats; Rats, Wistar; Receptor, Muscarinic M3; Sjogren's Syndrome; Sodium-Potassium-Exchanging ATPase; Submandibular Gland; Tropicamide; Xerostomia

1. Using rats, we examined the muscarinic receptor subtype mediating pilocarpine-induced parotid salivary secretion and the contributions of ion transporter systems (effluxes of K+ and Cl(-)) and aquaporin-5 (AQP5) translocation to this response in parotid glands in irradiated-induced xerostomia. 2. Salivary secretion was significantly lower in irradiated compared with sham-irradiated (normal) rats. In xerostomia rats, 0.4 and 0.8 mg/kg pilocarpine significantly increased parotid salivary secretion, although the salivary volume was still significantly less than in normal rats after the same dose of pilocarpine. 3. Pirenzepine (1 x 10(-6) to 1 x 10(-1) mol/L), AF-DX 116 (3 x 10(-6) to 3 x 10(-2) mol/L) and N-2-chloroethyl-4-piperidinyl diphenylacetate (4-DAMP; 1 x 10(-8) to 1 x 10(-2) mol/L) dose-dependently displaced radioligand binding to M(1), M(2) and M(3) receptors, respectively, in parotid membranes from both normal and irradiated rats. In each group of rats, 4-DAMP had the highest binding affinity. Pretreatment with 4-DAMP or pirenzepine dose-dependently inhibited pilocarpine-induced parotid secretion in both normal and irradiated rats, with 4-DAMP being markedly more potent than pirenzepine. 4. Normal and irradiated-rat parotid cells did not differ significantly in terms of pilocarpine-induced changes in [Ca2+](i), [K+](i) and [Cl(-)](i). Pilocarpine markedly increased the amount of AQP5 in the apical plasma membrane of parotid cells isolated from normal but not irradiated rats. 5. Thus, pilocarpine induces parotid salivary secretion mainly via the M(3) receptor subtype in both irradiated and normal rats. The reduction in this pilocarpine-induced secretion seen in irradiated rats is due not to disturbances of intracellular Ca2+ mobilization or ion transporter systems, but rather to a disturbance of AQP5 translocation, which may be involved in the pathogenesis of X-ray irradiation-induced xerostomia.

Topics: Animals; Aquaporin 5; Calcium; Male; Muscarinic Agonists; Muscarinic Antagonists; Parotid Gland; Pilocarpine; Piperidines; Protein Transport; Radiation Injuries, Experimental; Radioligand Assay; Rats; Rats, Sprague-Dawley; Saliva; Salivation; Whole-Body Irradiation; Xerostomia

Pirmenol hydrochloride, a novel pyridinemethanol derivative, is a long-acting class Ia antiarrhythmic agent. Preclinical toxicology data were obtained in rat, mouse, dog and rabbit. In acute toxicity studies by oral and intravenous routes, no pathologic changes were observed in surviving mice, rats and dogs. In repeated dose toxicity studies, no drug-related pathologic changes were evident; dryness of the oral mucosa in dogs and body weight gain reductions in rodents were the only significant clinical signs. In a chronic (52 week) toxicity study in rats, pirmenol given in the diet was tolerated clinically at doses up to 100 mg/kg/day. No drug-related aberrations in clinical laboratory parameters or ophthalmic or pathologic findings were evident. In a similar study in beagle dogs, pirmenol was tolerated clinically at a dosage up to 30 mg/kg/day. No significant changes in biochemical, hematologic, urinary or bone marrow determinations were found in either species. In reproductive toxicology studies in rats, pirmenol had no significant effect on litter size or embryonic viability. In rabbits pirmenol had no effect on average litter size, embryonic viability or fetal wastage. Given to male rats, pirmenol had no overt effects on fertility. Pirmenol failed to elicit deoxyribonucleic acid damage or induce cytogenetic alterations. Pirmenol appears to be without significant limiting toxicologic properties.

Topics: Administration, Oral; Animals; Anti-Arrhythmia Agents; Dogs; Female; Fetus; Injections, Intravenous; Male; Mice; Mice, Inbred Strains; Piperidines; Pregnancy; Pregnancy, Animal; Rabbits; Rats; Rats, Inbred Strains; Reproduction; Species Specificity; Xerostomia

Flecainide, a new antiarrhythmic agent, was given to eight healthy men to ascertain plasma drug levels and to assess tolerance for the drug. Each subject received a single intravenous (IV) dose (0.5, 1, 1.5, or 2 mg/kg) of flecainide, and plasma levels of unchanged flecainide were measured by gas-liquid chromatography. After an initial rapid distribution phase, the drug's plasma half-life (terminal elimination phase) ranged from seven to 15 hours (mean, 11 hours); half-life was apparently independent of dose level. Immediately after IV administration, the relatively high plasma drug levels seen during the short distribution phase were associated with minor and transient side effects in some subjects receiving the two higher doses; overall, the drug was well tolerated. Plasma flecainide levels 60 minutes after administration (after distribution) ranged from 52 to 300 ng/ml and were reasonably proportional to dose level. The drug's relatively long plasma half-life in humans indicates that plasma levels will be maintained for prolonged periods; thus flecainide should provide sustained therapeutic activity in patients with cardiac arrhythmias.

Topics: Adult; Anti-Arrhythmia Agents; Chromatography, Gas; Dizziness; Drug Tolerance; Electrocardiography; Flecainide; Half-Life; Humans; Male; Piperidines; Vision, Ocular; Xerostomia