Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MF-268 bitartrate [(3a S, 8a R)-1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethylpyrrolo[2,3-b]indol- 5-ol[8-(cis2,-6-dimethyl-morpholin-4-yl)octyl]-carbamate L-bitartrate hydrate; Mediolanum Farmaceutici, Milan, Italy] is a pseudo-reversible carbamate-type cholinesterase inhibitor (ChEI) which interacts with the catalytic and regulatory anionic site of the enzyme. Its effects on extracellular levels of acetylcholine (ACh), norepinephrine (NE), dopamine (DA), and serotonin (5-HT, 5-hydroxytryptamine) were studied in rat cortex by using a microdialysis technique coupled with high-performance liquid chromatography-electrochemical detection (HPLC-ECD). Conscious, freely moving rats were systemically [per os (p.o.) and subcutaneously (s.c.)] administered MF-268 with no ChEI in the probe. Cholinesterase inhibition in brain was assayed in parallel experiments. Oral administration of MF-268 (0.5, 2.0, and 5.0 mg/kg) produced a significant increase of extracellular ACh in cortex; the maximal increase was 300% [not significant (n.s.)], 460% and 1,200%, respectively. Maximal cholinesterase (ChE) inhibition was 2.3% (n.s.) at 9 hr and 9.7% (P < .05) at 12 hr after the 2.0 and 5.0 mg/kg doses, respectively. Norepinephrine and DA levels were increased 180% and 100% after the 5.0 mg/kg dose, respectively; 100% and 60% after the 2.0 mg/kg dose, respectively; and 70% for both amines after the 0.5 mg/kg dose, respectively. The elevation lasted at least 5 hr with the 2.0 and 5.0 mg/kg doses. There were no major changes in 5-HT levels at these three doses. Subcutaneous administration (0.5 and 2.0 mg/kg) produced a maximal 360% (5.5 hr) and 2,500% (5 hr) increase in extracellular ACh, respectively. Maximal ChE inhibition was 13% (0.5 mg/kg) and 41% (2.0 mg/kg). Neither 0.5 nor 2.0 mg/kg produced a consistent modification of NE. Only a transient increase in DA was seen with the 0.5 mg/kg dose. There were no changes in 5-HT levels at these two doses. MF-268-treated animals showed slight cholinergic side effects (chewing, tremor) at both doses. MF-268 administered intracortically through the microdialysis probe at a concentration of 50 microM induced a 5,900% increase in ACh levels at 6 hr. This effect started 30 min after injection and continued throughout the period of administration. MF-268 produced a significant decrease in NE levels (-44%) starting at 30 min, and a slight but significant increase in DA levels of 45% at 2.5 hr. A significant increase of 5-HT (58%) was also observed starting at 4 hr. Slight symptoms of cholinergic toxicity were observed during intracortical administration.
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PMID:Effects of MF-268, a new cholinesterase inhibitor, on acetylcholine and biogenic amines in rat cortex. 883 83

Disulfiram (Antabuse) is used for aversive treatment of alcohol dependence with good effects. Through inhibition of aldehyde dehydrogenase, disulfiram heightens serum aldehyde concentration after alcohol ingestion and causes aversive disulfiram-ethanol reaction. Typical symptoms of this reaction include flushing, nausea, dyspnea, tremor, and confusion, which are usually self-limiting. However, severe life-threatening arterial hypotension sometimes develops. We report here a patient with generalized flushing, tremor, and refractive hypotension after ingestion of alcohol 18 hours after disulfiram treatment. Initial volume resuscitation and dopamine infusion failed to restore the blood pressure. Noradrenaline was given and the blood pressure returned to normal range. This case illustrates the intensity of disulfiram-ethanol reaction and underscores the advantageous use of noradrenaline in patients in such a critical condition.
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PMID:Refractive hypotension in a patient with disulfiram-ethanol reaction. 1722 Jun 94

Ten cases of pheochromocytoma in horses were obtained from the literature and a computer search of medical records. The clinical, laboratory and pathological features of pheochromocytoma in horses were reviewed. Pheochromocytoma is a catecholamine secreting tumor which tends to occur in older horses without breed or sex predisposition. It is usually unilateral adrenal medullary in location and benign. Malignancy was present in one horse. The most common clinical signs were sweating, tachycardia, tachypnea, muscle tremor and anxiety; however the tumor may be asymptomatic. Clinical signs were nonspecific and could be confused with other diseases, especially abdominal pain. Hyperglycemia is a consistent finding. Venous norepinephrine levels were measured in normal horses. Norepinephrine measurements may prove to be a diagnostic aid in horses with pheochromocytoma.
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PMID:Pheochromocytoma in the horse and measurement of norepinephrine levels in horses. 1742 50


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