Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 13-week oral repeated dose toxicity study of Suplatast tosilate (IPD-1151T), a new anti-allergic agent, as well as a 5-week recovery study were carried out at dose levels of 0 (control), 200, 600, 1800 and 5400 mg/kg/day using male and female rats. The results were as follows: 1. In general conditions, salivation were observed in some rats of both sexes given 1800 mg/kg/day. Both sexes given 5400 mg/kg/day disclosed salivation and soft stool and then died after showing ataxic gait, hyperesthesia and convulsion of legs. 2. Inhibition of body weight gain in both sexes given 5400 mg/kg/day were observed from the early stage of the treatment period. 3. The food consumption was decreased from about 3-week and the water consumption was increased from the initiation of study to about 3-week in both sexes given 5400 mg/kg/day. However, both of them were remarkably decreased prior to death. 4. Fecal examination for occult blood showed an increasing tendency in the incidence of positive findings in both sexes given 1800 mg/kg/day. 5. Hematological examination showed slight decreases in erythrocytic parameters in both sexes given 1800 mg/kg/day. In both sexes given 5400 mg/kg/day hemoconcentration was observed, some animals showing decreases in leucocyte and lymphocyte counts and lymphocyte percentage. 6. Biochemical examination showed increases in total and free cholesterol levels in males given 600 mg/kg/day or more, an increased cholinesterase and decreased levels of triglyceride and cholesterol ester ratio in males given 1800 mg/kg/day. An increase in LDH was observed in both sexes given 5400 mg/kg/day and half of these animals also showed increases in GOT and Urea N. 7. The absolute weights of the pituitary, brain, thymus, heart, lungs and kidneys were increased. However, no histopathological lesion was observed in these organs. As treatment-related histological changes, atrophy in the thymus and spleen, dilation in digestive tracts, neuronal necrosis and necrotic foci in the central nervous system, necrosis of lymphocytes in the lymphoid organs and a decrease in bone marrow cell were observed in both sexes given 5400 mg/kg/day. 8. After a 5-week recovery period, above-mentioned changes had disappeared. 9. From the above results, the non-effective dose level was estimated to be 200 mg/kg/day in males and 600 mg/kg/day in females, and toxic dose level 1800-5400 mg/kg/day in both sexes.
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PMID:[A thirteen-week oral repeated dose toxicity study of suplatast tosilate (IPD-1151T) in rats]. 132 Dec 57

Targeting analgesic drugs for spinal delivery reflects the fact that while the conscious experience of pain is mediated supraspinally, input initiated by high intensity stimuli, tissue injury and/or nerve injury is encoded at the level of the spinal dorsal horn and this output informs the brain as to the peripheral environment. This encoding process is subject to strong upregulation resulting in hyperesthetic states and downregulation reducing the ongoing processing of nociceptive stimuli reversing the hyperesthesia and pain processing. The present review addresses the biology of spinal nociceptive processing as relevant to the effects of intrathecally-delivered drugs in altering pain processing following acute stimulation, tissue inflammation/injury and nerve injury. The review covers i) the major classes of spinal agents currently employed as intrathecal analgesics (opioid agonists, alpha 2 agonists; sodium channel blockers; calcium channel blockers; NMDA blockers; GABA A/B agonists; COX inhibitors; ii) ongoing developments in the pharmacology of spinal therapeutics focusing on less studied agents/targets (cholinesterase inhibition; Adenosine agonists; iii) novel intrathecal targeting methodologies including gene-based approaches (viral vectors, plasmids, interfering RNAs); antisense, and toxins (botulinum toxins; resniferatoxin, substance P Saporin); and iv) issues relevant to intrathecal drug delivery (neuraxial drug distribution), infusate delivery profile, drug dosing, formulation and principals involved in the preclinical evaluation of intrathecal drug safety.
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PMID:Current and Future Issues in the Development of Spinal Agents for the Management of Pain. 2686 70