Cholinergic agent

Many AD patients, especially those in advanced stages of the disorder, suffer from serious behavioral and psychiatric symptoms of dementia (acronym BPSD), making their own life and that of their family or professional caregivers difficult. Studies in institutionalized AD patients with BPSD indicate 

Chemical class Piperidine Carbamate Phenanthrene alkaloid 

Origin Synthetic compound Synthetic compound Natural product (from the flower snowdrop) 

Enzymes inhibited Acetylcholinesterase (AChE) AChE, butyryl-cholinesterase (BuChE) AChE 

Inhibition type Rapidly reversible Slowly reversible Rapidly reversible 

---

Potential oscillation was measured in the presence of cholinergic agents (acetylcholine chloride, carbamylcholine chloride, carbamyl- d-methylcholine chloride, and acetyl-/6-methylcholine chloride) and anticholinergic agents (tetramethylammonium chloride, tetra-ethylammonium chloride, succinylcholine chloride, hexamethonium chloride, scopolamine hydrobromide, atropine sulfate, homatropine hydrochloride, and tubocurarine chloride)... 

Finnegan, K. Kanner, M. and Meltzer, H.Y. Phencyclidine-induced rotational behavior in rats with nigrostriata 1 lesions and its modulation by dopaminergic and cholinergic agents. Pharmacol Biochem Behav 5 651-660, 1976. 

Bisoxatin Acetate Choleretic Piprozolin Cholinergic Agent Aceclidine Coccidiostats Oxyphenisatin Acetate... 

Arevalo, J.I. and Saz, H.J. (1992) Effects of cholinergic agents on the metabolism of choline in muscle from Ascaris suum. Journal of Parasitology 78, 387-392. 

There has only been one detailed conformational study on azoniaspirocycles using NMR spectroscopy. Aitken etal. <2002ARK63> have reported the NMR data ( H 300 MHz, 13C at 75 MHz) for compounds previously determined to be novel cholinergic agents for the control of blood pressure 9-12 <1954JA5099, 1954JA2427>. 

The allylic C-H functionalization has been effectively used for the syntheses of pharmaceutical targets. The reaction of the 3,4-dichlorophenyl derivative 11 with 1,4-cyclohexadiene generated the C-H insertion product 12 with 93% ee, which was then readily converted to (+)-indatraline using conventional chemistry (Equation (29)).88 The thiophenyl derivative 13 was also capable of a C-H insertion to form 14 with 88% ee. A few trivial steps converted 14 to the cholinergic agent (+)-cetiedil (Equation (30)).89... 

Costa LG, Kaylor G, Murphy SD. 1990. In vitro and in vivo modulation of cholinergic muscarinic receptors in rat lymphocytes and brain by cholinergic agents. Int J Immunopharmacol 12 67-75. 

Sunderland T, Tariot PN, Newhouse PA. (1988). Differential responsivity of mood, behavior, and cognition to cholinergic agents in elderly neuropsychiatric populations. Brain Res. 472 4y. 371-89. Tachikawa E, Kudo K, Flarada K, Kashimoto T, Miyate Y, Kakizaki A, Takahashi E. (1999). Effects of ginseng saponins on responses induced by various receptor stimuli. EurJ Pharmacol 369(1) 23-32. Tagami M, Ikeda K, Yamagata K, Nara Y, Fujino FI, Kubota A, Numano F, Yamori Y. (1999). Vitamin E prevents apoptosis in hippocampal neurons caused by cerebral ischemia and reperfusion in stroke-prone spontaneously hypertensive rats. Lab Invest. 79(5) 609-15. 

Atropine (Various) Cholinergic agents Organophosphates, carbamates, pilocarpine, physostigmine, or choline esters. 

Uses Minimize paralytic ileus, Rx postop distention Action Cholinergic agent Dose Adults. Relief of gas 2-3 tabs PO tid Prevent postop ileus 250-500 mg IM stat, repeat in 2 h, then q6h PRN Ileus 500 mg IM stat, repeat in 2 h, then q6h, PRN Caution [C, ] Contra Hemophilia, mechanical bowel obst Disp Inj, tabs, cream SE GI cramps EMS May cause bowel obstruction, monitor pt for abd pain and inquire about recent bowel habits OD Sxs unknown symptomatic and supportive... 

The inherent anticholinergic properties of procainamide may interfere with the therapeutic effect of cholinergic agents. Patients receiving cimetidine and procainamide may exhibit signs of procainamide toxicity, as cimetidine inhibits the metabolism of procainamide. Simultaneous... 

Treafmenf should consisf of gasfric lavage, emefics, and activated charcoal, if indicated, parenteral cholinergic agents such as physostigmine or bethanechol chloride should be added. 

Mechanism of Action A cholinergic agent that prevents destruction of acetylcholine byinhibitingthe enzyme acetylcholinesterase, thus enhancing impulse transmission across the myoneural junction. Therapeutic Effect Produces miosis increases intestinal, skeletal muscle tone stimulates salivary and sweat gland secretions. Pharmacokinetics Not protein bound. Excreted unchanged in urine. Half-life Unknown. 

Spirocyclic 2,4-oxazolidinedione analogues have been prepared and evaluated as cholinergic agents by Japanese workers (Scheme 6.52). For example, condensation of the a-hydroxy ester 226 with urea produced 227a quantitatively, whereas reaction with thiourea afforded 227b in poor yield together with 228. 

It is a cholinergic agent because it promotes the synthesis and freeing of acetylcholine. 

---