Disease relevance of Talsaclidine

• A higher dose of talsaclidine (4.7 mg/kg) resulted in side effects (lethargy and excessive drooling) in some animals [1].
• Ipratropium bromide, a peripheral antimuscarinic drug, reversed this hypotensive action of intravenous talsaclidine into hypertension, but did not inhibit the effects of central administration [2].
• Intravenous injection of 1-64 mg/kg talsaclidine did not cause substantial bronchospasm in control animals [3].
• The aim of the present investigation was to determine the reasons why the muscarinic receptor agonist talsaclidine (WAL 2014 FU, 1-azabicyclo[2.2.2] octane,3-(2-propynyloxy)-, (R)-,(E)-2-butenedioate) is devoid of bronchospastic effects in anaesthetized guinea pigs but causes contracture in isolated tracheal muscle from this species [3].
• In this study, we show that the m1-selective agonist talsaclidine concentration-dependently increased APPs release from both transfected human astrocytoma cell lines and rat brain slices [4].

Psychiatry related information on Talsaclidine

• Memory-related task performance by aged rhesus monkeys administered the muscarinic M(1)-preferring agonist, talsaclidine [1].
• Talsaclidine, a novel M1-receptor selective muscarinic agonist for cholinergic substitution therapy of Alzheimer's disease, activates the sympathetic nervous system in guinea pigs and dogs at the orthosympathic ganglia and the paraganglionic adrenals [2].

High impact information on Talsaclidine

• Stimulation of cells with the M1/M3-selective mAChR agonist talsaclidine for 1 hr resulted in a dose-dependent increase in BACE1 expression up to twofold over basal levels [5].
• The results demonstrate that talsaclidine, a selective muscarinic M1-receptor agonist, activates central parts of the sympathetic nervous system, including central projections of the adrenals by an action mediated by central muscarinic receptors [2].
• The present investigation in anaesthetized and vagotomized guinea pigs intended to demonstrate central activation of the sympathetic nervous system directly by comparing the blood pressure effects of intracerebroventricular and intravenous injections of small doses of talsaclidine [2].
• Studies from other labs showed that AF102B and talsaclidine (another M1 agonist) decreased cerbrospinal fluid (CSF) Abeta in AD patients following chronic treatment, being the first reported drugs with such a profile [6].
• We compared cerebrospinal fluid (CSF) levels of A beta 40 and A beta 42 measured by ELISA before and at the end of 4 weeks of treatment with talsaclidine [7].

Biological context of Talsaclidine

• Pharmacokinetics of the M1-agonist talsaclidine in mouse, rat, rabbit and monkey, and extrapolation to man [8].

Anatomical context of Talsaclidine

• Talsaclidine was administered double-blind, placebo-controlled, and randomized to 24 AD patients and cerebrospinal fluid (CSF) levels of total A beta were quantitated before and after 4 weeks of drug treatment [9].
• It is concluded that the sympathetic activation by talsaclidine is due to full agonism at the M1-receptor and the ability to cross the blood-brain barrier [10].

Associations of Talsaclidine with other chemical compounds

• The aim of this investigation in anaesthetized dogs was to provide direct evidence for an activation of the sympathetic nervous system by the muscarinic agonist talsaclidine (WAL 2014 FU) [10].

Gene context of Talsaclidine

• Treatment with the selective muscarinic agonist talsaclidine decreases cerebrospinal fluid levels of total amyloid beta-peptide in patients with Alzheimer's disease [9].

Analytical, diagnostic and therapeutic context of Talsaclidine

• In both groups central administration of talsaclidine caused dose-related hypertension while intravenous injections were hypotensive [2].
• The hypertensive effect of a first injection of 0.6 mg/kg talsaclidine into the cisterna cerebellomedullaris of 6 guinea pigs was approximately twice as large as that of a second given 90 min after bilateral adrenalectomy [2].
• The mean difference between CSF levels of A beta 42 before and after treatment with talsaclidine (n = 34) was -46 +/- 73 (SD) pg/ml as compared to 0 +/- 8 (SD) pg/ml with placebo (n = 6) (p < 0.05) [7].

References