Parkinson's disease is one of the most common neurodegenerative disorders world widely. Although curable therapies are practically not available yet, symptomatic managements using anti-Parkinson medications have shown to be quite effective to improve patients' quality of life. The discovery of dopaminergic deficits in Parkinson's disease in 1960s have brought about the human clinical trials of levodopa, which opened an “Era of Dopamine” in treatment history of the Parkinson's disease. Levodopa still remains gold standard. Dopamine agonists have proved their efficacies and delayed the development of long-term complications of levodopa use. Inhibitors of respective enzyme monoamine oxidase-B and catechol-O-methyltransferase, anticholinergics, and amantadine strengthen the therapeutic effects via either monotherapy or adjunctive way. Strategy of continuous dopaminergic stimulation and disease modification are weighing in current advances. This article is providing evidence-based review of pharmacological treatment of Parkinson's disease from early to advanced stages as well as management its unavoidable adverse reactions.
Amantadine ; Catechol O-Methyltransferase ; Cholinergic Antagonists ; Dopamine Agonists ; Drug Therapy ; Humans ; Levodopa ; Neurodegenerative Diseases ; Parkinson Disease ; Quality of Life ; Therapeutic Uses

BACKGROUND/AIMS: Gastric peristalsis begins in the orad corpus and propagates to the pylorus. Directionality of peristalsis depends upon orderly generation and propagation of electrical slow waves and a frequency gradient between proximal and distal pacemakers. We sought to understand how chronotropic agonists affect coupling between corpus and antrum. METHODS: Electrophysiological and imaging techniques were used to investigate regulation of gastric slow wave frequency by muscarinic agonists in mice. We also investigated the expression and role of cholinesterases in regulating slow wave frequency and motor patterns in the stomach. RESULTS: Both acetycholinesterase (Ache) and butyrylcholine esterase (Bche) are expressed in gastric muscles and AChE is localized to varicose processes of motor neurons. Inhibition of AChE in the absence of stimulation increased slow wave frequency in corpus and throughout muscle strips containing corpus and antrum. CCh caused depolarization and increased slow wave frequency. Stimulation of cholinergic neurons increased slow wave frequency but did not cause depolarization. Neostigmine (1 muM) increased slow wave frequency, but uncoupling between corpus and antrum was not detected. Motility mapping of contractile activity in gastric muscles showed similar effects of enteric nerve stimulation on the frequency and propagation of slow waves, but neostigmine (> 1 muM) caused aberrant contractile frequency and propagation and ectopic pacemaking. CONCLUSIONS: Our data show that slow wave uncoupling is difficult to assess with electrical recording from a single or double sites and suggest that efficient metabolism of ACh released from motor neurons is an extremely important regulator of slow wave frequency and propagation and gastric motility patterns.
Animals ; Cholinergic Neurons ; Cholinesterases* ; Metabolism ; Mice* ; Motor Neurons ; Muscarinic Agonists ; Muscle, Smooth ; Muscles ; Neostigmine ; Peristalsis ; Pylorus ; Stomach

To investigate the mechanisms underlying the cholinergic agonist carbachol-induced cardiovascular responses, changes of renin-angiotensin system were examined in fetal hormonal systems. In the ovine fetal model under stressless condition, the cardiovascular function was recorded. Blood samples were collected before (during baseline period) and after the intravenous administration of carbachol. Simultaneously, the levels of angiotensin I (Ang I), angiotensin II (Ang II) and vasopressin in the fetal plasma were detected by immunoradiological method. Also, blood gas, plasma osmolality and electrolyte concentrations were analyzed in blood samples. Results showed that in chronically prepared ovine fetus, intravenous infusion of carbachol led to a significant decrease of heart rate (P < 0.05), and a transient decrease followed by an increase of blood pressure (P < 0.05) within 30 min. After the intravenous infusion of carbachol, blood concentrations of Ang I and Ang II in near-term ovine fetus were both significantly increased (P < 0.05); however, blood concentration of vasopressin, values of blood gas, electrolytes and plasma osmolality in near-term ovine fetus were not significantly changed (P > 0.05). Blood levels of Ang I and Ang II in the atropine (M receptor antagonist) + carbachol intravenous administration group was lower than those in the carbachol group without atropine administration (P < 0.05). In conclusion, this study indicates that the near-term changes of cardiovascular system induced by intravenous administration of carbachol in ovine fetus, such as blood pressure and heart rate, are associated with the changes of hormones of circulatory renin-angiotensin system.
Angiotensin I ; blood ; Angiotensin II ; blood ; Animals ; Blood Pressure ; Carbachol ; pharmacology ; Cholinergic Agonists ; pharmacology ; Fetus ; Heart Rate ; Renin-Angiotensin System ; Sheep ; Vasopressins ; blood

Adrenergic beta-Agonists ; therapeutic use ; Aged ; Androstadienes ; therapeutic use ; Cholinergic Antagonists ; therapeutic use ; Fluticasone ; Humans ; Male ; Middle Aged ; Scopolamine Derivatives ; therapeutic use ; Silicosis ; drug therapy ; Tiotropium Bromide

Animals ; Arecoline ; pharmacology ; Cholinergic Agonists ; pharmacology ; Female ; Guinea Pigs ; In Vitro Techniques ; Male ; Muscle Contraction ; drug effects ; Muscle, Smooth ; physiology ; Pyloric Antrum ; physiology ; Receptor, Muscarinic M3 ; metabolism

BACKGROUNDCa(2+) in the central nervous system plays important roles in brain physiology, including neuronal survival and regeneration in rats with injured facial motoneurons. The present research was to study the modulations of intracellular free Ca(2+) concentrations by cholinergic receptors in rat facial nucleus, and the mechanisms of the modulations.

METHODSThe fluorescence intensity of facial nucleus in Fluo-3 AM loaded acute brainstem slices was detected by applying intracellular free Ca(2+) measurement technique via confocal laser scanning microscope. The changes of fluorescence intensity of facial nucleus indicate the average changes of intracellular free Ca(2+) levels of the neurons.

RESULTSAcetylcholine was effective at increasing the fluorescence intensity of facial nucleus. Muscarine chloride induced a marked increase of fluorescence intensity in a concentration dependent fashion. The enhancement of fluorescence intensity by muscarine chloride was significantly reduced by thapsigargin (depletor of intracellular Ca(2+) store; P < 0.01), rather than Ca(2+) free artifical cerebrospinal fluid or EGTA (free Ca(2+) chelator; P > 0.05). And the increase of fluorescence intensity was also significantly inhibited by pirenzepine (M(1) subtype selective antagonist; P < 0.01) and 4-DAMP (M(3) subtype selective antagonist; P < 0.01). In addition, fluorescence intensity was markedly increased by nicotine. The enhancement of fluorescence intensity by nicotine was significantly reduced by EGTA, nifedipine (L-type voltage-gated Ca(2+) channel blocker), dihydro-beta-erythroidine (alpha4beta2 subtype selective antagonist), and in Ca(2+) free artificial cerebrospinal fluid (P < 0.01), but not in the presence of mibefradil (M-type voltage-gated Ca(2+) channel blocker) or thapsigargin (P > 0.05).

CONCLUSIONSThe data provide the evidence that muscarinic receptors may induce the increase of intracellular free Ca(2+) levels through the Ca(2+) release of intracellular Ca(2+) stores, in a manner related to M(1) and M(3) subtypes of muscarinic receptors in rat facial nucleus. Nicotine may increase intracellular free Ca(2+) concentrations via the influx of extracellular Ca(2+)+ mainly across L-type voltage-gated Ca(2+) channels, in a manner related to the alpha4beta2 subtype of nicotinic receptors.

Acetylcholine ; pharmacology ; Aniline Compounds ; administration & dosage ; Animals ; Brain Stem ; cytology ; drug effects ; metabolism ; Calcium ; metabolism ; Diamines ; pharmacology ; Facial Nerve ; cytology ; Female ; Fluorescent Dyes ; administration & dosage ; In Vitro Techniques ; Male ; Microscopy, Confocal ; Motor Neurons ; drug effects ; metabolism ; Muscarinic Agonists ; pharmacology ; Nicotine ; pharmacology ; Nicotinic Agonists ; pharmacology ; Piperidines ; pharmacology ; Pirenzepine ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Cholinergic ; metabolism ; Receptors, Muscarinic ; metabolism ; Receptors, Nicotinic ; metabolism ; Tropicamide ; pharmacology ; Xanthenes ; administration & dosage

Acetylcholine ; metabolism ; physiology ; Animals ; Cholinergic Agonists ; pharmacology ; Male ; Muscle Contraction ; drug effects ; physiology ; Muscle Relaxation ; drug effects ; physiology ; Muscle, Smooth ; drug effects ; pathology ; physiopathology ; Rabbits ; Random Allocation ; Receptors, Cholinergic ; physiology ; Synaptic Transmission ; drug effects ; Urinary Bladder ; drug effects ; innervation ; physiopathology

OBJECTIVETo investigate the effects of arecoline and nicotine on the expression of human telomerase reverse transcriptase (hTERT) mRNA and protein in cultured normal human oral keratinocytes (KC).

METHODSThe experiments were divided into arecoline group, arecoline/nicotine group and control group. The hTERT mRNA and protein expression of KC was examined by reverse transcription polymerase chain reaction (RT-PCR) and Western blot.

RESULTSArecoline could induce the hTERT mRNA and protein expression of KC in a dose dependent manner, the hTERT mRNA and protein expression of KC was higher in 0.030, 0.060, 0.090 g/L arecoline group than control group (P < 0.001). Nicotine (0.025 g/L) increased hTERT mRNA and protein expression of KC induced by arecoline.

CONCLUSIONSArecoline could increase the expression of hTERT mRNA and protein in oral keratinocytes. Nicotine had a synergistic effect on arecoline. hTERT over-expression induced by arecoline and nicotine may play an important role in the malignant transformation of oral submucous fibrosis.

Arecoline ; pharmacology ; Cells, Cultured ; Cholinergic Agonists ; pharmacology ; Dose-Response Relationship, Drug ; Drug Synergism ; Ganglionic Stimulants ; pharmacology ; Humans ; Keratinocytes ; drug effects ; enzymology ; Mouth Mucosa ; enzymology ; pathology ; Nicotine ; pharmacology ; RNA, Messenger ; genetics ; metabolism ; Telomerase ; genetics ; metabolism

Urinary incontinence is an important lower urinary tract symptom that negatively affects the quality of life. Urgency incontinence (UI) is urine loss accompanied by urgency, which is the chief complaint of overactive bladder (OAB) syndrome. OAB is defined as urgency, with or without UI, usually with frequency and nocturia. In contrast, stress urinary incontinence (SUI) involves involuntary urine leakage caused by a sudden increase in abdominal pressure. Treatment for urinary incontinence depends on the type of incontinence, the severity, and the underlying causes. Treatment options fall into four broad categories: lifestyle intervention, bladder retraining and/or pelvic floor muscle training, pharmacotherapy, and surgery. Pharmacotherapy is often the first-line therapy for OAB/UI, either alone or as an adjunct to various nonpharmacological therapies. Effectiveness of anticholinergic drugs for OAB/UI has been assessed in various observational and randomized controlled trials. Despite their side effects, anticholinergics are the first-line agents for UI. Tricyclic antidepressants have complex pharmacological actions such as anticholinergic, alpha adrenergic, antihistaminic, and local anesthetic properties. Recently approved anticholinergics, solifenacin and darifenacin, are selective M3 antagonists that may have tolerable side effects. Transdermal oxybutynin may offer comparable efficacy with oral formulation but lower side effects. In the absence of an effective and well tolerated drug for SUI, pharmacological therapy for this condition has remained in the off-label prescription of some products, particularly estrogens and alpha-adrenergic agonists. Duloxetine is the drug of choice specifically aimed at SUI. This article outlines the current state and future development in pharmacological therapy for urinary incontinence.
Adrenergic alpha-Agonists ; Antidepressive Agents, Tricyclic ; Cholinergic Antagonists ; Drug Therapy ; Duloxetine Hydrochloride ; Estrogens ; Life Style ; Nocturia ; Pelvic Floor ; Prescriptions ; Quality of Life ; Solifenacin Succinate ; Urinary Bladder ; Urinary Bladder, Overactive ; Urinary Incontinence* ; Urinary Tract

Acetylcholine ; metabolism ; Animals ; Brain ; drug effects ; metabolism ; Choline O-Acetyltransferase ; metabolism ; Cholinergic Agonists ; pharmacology ; Epithelial Cells ; metabolism ; Kidney Tubules ; cytology ; metabolism ; Lateral Ventricles ; drug effects ; Male ; Natriuresis ; Rats ; Rats, Sprague-Dawley