Salivary secretion stimulation

Another clinically important effect I would like to mention is the inhibition of salivary secretion by clonidine. Both the sympathetic nervous system and the parasympathetic nervous system are involved in the physiological regulation of salivation. HOEFKE (53) as well as RAND and coworkers (54) found that parasympathetic salivary secretion stimulated by electrical impulses on the chorda tympani and by carbachol could not be blocked by clonidine in anaesthetised animals. In our own experiments in rats with clonidine and the 2,6-diethyl derivative St 91 which does not penetrate to the CNS, secretion of saliva was blocked only after clonidine, (HOEFKE (55)) indicating a central mode of action. 

Utilize nontoxic excipients (both diluents and the mucoadhesive polymers) which do not irritate or damage the mucosa and do not stimulate salivary secretion. 

Pharmacology Solifenacin is a competitive muscarinic receptor antagonist. Muscarinic receptors plays a role in contractions of urinary bladder smooth muscle and stimulation of salivary secretion. 

Certain stimulant actions of catecholamines on various smooth muscles are blocked by alpha blockers such as uterine contraction of certain species, contraction of vas deferens and retractor penis, stimulation of seminal vesicles and vas deferens. Alpha blockers can inhibit ejaculation and produce impotence. Salivary secretion and sweat formation induced by catecholamines is blocked by alpha blockers. 

Other actions In the gastrointestinal tract, acetylcholine increases salivary secretion, and stimulates intestinal secretions and motility. Bronchiolar secretions are also stimulated. In the genitourinary tract, the tone of the detrusor urinae muscle is increased. In the eye, acetylcholine is involved in stimulating ciliary muscle contraction for near vision and in the constriction of the pupillae sphincter muscle, causing miosis (marked constriction of the pupil). 

Anticholinesterases such as malathion are used in commercial insecticide sprays. Unprotected operators may absorb malathion via the eyes, skin, respiratory tract and mucous membranes of the mouth. Effects include intestinal cramps and diarrhoea following stimulation of intestinal motility and secretion. Stimulation of lacrimal and salivary glands causes the eyes to water profusely (lacrimation) and saliva to drool. Bradycardia, bronchoconstriction, dyspnoea and increased sweating also occur. Skeletal muscle twitching (fasciculation) is due to the prolonged action of released acetylcholine at the skeletal neuromuscular junction. 

Substance P is an 11-amino-acid peptide amide hormone discovered by von Euler and Gaddum in 1931 (43) from certain tissue extracts, especially from intestinal plain muscles and brains of horses. It is involved in the transmission of pain impulses from peripheral receptors to the central nervous system. It is also involved in the vomit reflex, stimulates salivary secretions, and induces vasodilation. Antagonists seem to have antidepressant properties. 

A major portion of saliva is composed of water (99%) and has a pH of 6.5-7.S depending on the flow rate and location.An increase in the salivary flow rate leads to the secretion of watery saliva. Stimulated salivary secretion affects the film thickness and aids in easy migration of test compounds from one region of the mouth to another. Salivary pH is also important because passive diffusion of unionized drug is the major mechanism of oral absorption. ... 

Vesicles containing proteins destined for intracellular use in lysosomes or outer membranes bud off from the trans face of the Golgi. Depending on their contents, some of the vesicles are diverted to nonsecretory vesicles by the presence of phosphomannose residues on their N-linked glycans or by possessing domains rich in hydrophobic amino acids. At the apical surface of salivary acini, the remaining vesicles accumulate as secretory vesicles. These vesicles become surrounded by myofibrils, which move the secretory vesicles to the cell membrane where they fuse and expel the saliva secretion into a small duct. The odor or taste of food provides a neuronal stimulus to the gland s myofibrils, and this stimulates salivary secretion. 

Tyramine (p-hydroxyphenethylamine) was isolated in 1909 by Barger and Dale (176) from Claviceps purpurea (ergot) and also by Henze (184) from the salivary gland of cephalopods. It provokes a salivary secretion, a contraction of the piloerectors, a mydriasis, and a slowing of the pulse rate in the dog (185). In the cat (0.06 g. subcutaneously) there can be noted, in addition, a motor stimulation, a respiratory excitation, and a hyperthermia (186), and in rats there is an increase in the respiratory volume (0.01-0.1 g. subcutaneously (187)). Bry (173) confirms the respiratory stimulation which tyramine provokes. 

Acetylcholine—the acetic ester of choline—has very strong and multiple biological actions. It excites or inhibits many organs and tissues in concentrations as low as 10" -10 ° even much higher sensitivity to ACh has been described. Dale divided the diverse effects of ACh into two large groups muscarinic and nicotinic effects. The muscarinic effects of ACh include its action on smooth muscle, for example its capacity to stimulate intestinal muscles or to cause a fall in blood pressure its inhibitory action on the cardiac pace-maker and muscles its action on the glands, the ability to induce salivary secretion, for instance. The muscarinic action of ACh resembles the effects of parasympathetic nerves it is reproduced by muscarine and blocked by atropine. 

Due to parasympathetic stimulation of the salivary glands, saliva is secreted continuously at a basal rate of approximately 0.5 ml/min. Secretion may be enhanced by two types of reflexes ... 

The simple or unconditioned salivary reflex occurs when food is present within the oral cavity and causes stimulation of chemoreceptors and pressure receptors. These receptors then transmit impulses to the salivary center in the medulla of the brainstem. Parasympathetic efferent impulses are transmitted back to the salivary glands and secretion is enhanced. 

Herbivores that commonly feed on tannin-rich plants have evolved interesting methods to lessen the effect of ingested tannins on their digestive systems. For example, the salivary proteins of rabbits and other rodents are high in the amino acid proline, which has a very high affinity for tannins. Eating food high in tannins stimulates the secretion of these proteins and diminishes the toxic effect of the tannins. 

Stimulation of saliva production is under sympathetic and parasympathetic control. Parasympathetic stimulation produces a serous watery secretion, whereas sympathetic stimulation produces much thicker saliva. Drug delivery systems, therefore, should not be placed over a duct or adjacent to a salivary duct, as this may dislodge the retentive system or may result in excessive wash-out of the drug or rapid dissolution/erosion of the delivery system making it difficult to achieve high local drug concentrations. If a retentive system is placed over salivary ducts, the reduced salivary flow rate may produce less or no mucus which is required for the proper attachment of a mucoadhesive delivery device. 

Histamine also evokes a copious secretion of highly acidic gastric juice from the gastric glands at doses below those that influence blood pressure (32). This effect of histamine is mediated through 2 receptors on the parietal cells. The importance of this effect in scombroid poisoning is not knowi. Histamine also has some stimulant actions on salivary, pancreatic, intestinal, bronchial, and lacrimal secretions (32), but these effects are relatively unimportant. 

In general, ethanol in low to moderate amounts, is relatively benign to most body systems. A moderate amount of ethanol causes peripheral vasodilation, especially of cutaneous vessels, and stimulates the secretion of salivary and gastric fluids the latter action may aid digestion. On the other hand, ethanol consumption in high concentrations, as found in undiluted spirits, can induce hemorrhagic lesions in the duodenum, inhibit intestinal brush border enzymes, inhibit the uptake of amino acids, and limit the absorption of vitamins and minerals. In addition, ethanol can reduce blood testosterone levels, resulting in sexual dysfunction. 

Mechanism of Action A cholinergic drug that prevents destruction of acetylcholine by inhibiting the enzyme acetylcholinesterase, thus enhancing impulse transmission across the myoneural junction. Therapeutic Effect Improves intestinal and skeletal muscle tone stimulates salivary and sweat gland secretions. 

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