Effect of chlormethiazole, dizocilpine and pentobarbital on harmaline-induced increase of cerebellar cyclic GMP and tremor. 1993

A J Cross, and A Misra, and A Sandilands, and M J Taylor, and A R Green
Astra Neuroscience Research Unit, London, UK.

Administration to mice of harmaline (100 mg/kg SC) resulted in a greater than two-fold increase in cyclic GMP in the cerebellum 15 min later. This response was inhibited by pretreatment 5 min before the harmaline with pentobarbital (ED50 6.5 mg/kg), chlormethiazole (ED50 10.4 mg/kg) and dizocilpine (ED50 0.5 mg/kg). Harmaline-induced tremor was inhibited by pentobarbital (ED50 30 mg/kg) and chlormethiazole (ED50 50 mg/kg) but not dizocilpine. The data demonstrate that the harmaline-induced tremor and cerebellar cyclic GMP rise are probably not associated. They also demonstrate that chlormethiazole is able to inhibit a biochemical response (the increase in cerebellar cyclic GMP) which results from increased glutamate function.

UI MeSH Term Description Entries
D008297 Male Males
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D010424 Pentobarbital A short-acting barbiturate that is effective as a sedative and hypnotic (but not as an anti-anxiety) agent and is usually given orally. It is prescribed more frequently for sleep induction than for sedation but, like similar agents, may lose its effectiveness by the second week of continued administration. (From AMA Drug Evaluations Annual, 1994, p236) Mebubarbital,Mebumal,Diabutal,Etaminal,Ethaminal,Nembutal,Pentobarbital Sodium,Pentobarbital, Monosodium Salt,Pentobarbitone,Sagatal,Monosodium Salt Pentobarbital
D002531 Cerebellum The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills. Cerebella,Corpus Cerebelli,Parencephalon,Cerebellums,Parencephalons
D002719 Chlormethiazole A sedative and anticonvulsant often used in the treatment of alcohol withdrawal. Chlormethiazole has also been proposed as a neuroprotective agent. The mechanism of its therapeutic activity is not entirely clear, but it does potentiate GAMMA-AMINOBUTYRIC ACID receptors response and it may also affect glycine receptors. Clomethiazole,Distraneurin
D006152 Cyclic GMP Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed) Guanosine Cyclic 3',5'-Monophosphate,Guanosine Cyclic 3,5 Monophosphate,Guanosine Cyclic Monophosphate,Guanosine Cyclic-3',5'-Monophosphate,3',5'-Monophosphate, Guanosine Cyclic,Cyclic 3',5'-Monophosphate, Guanosine,Cyclic Monophosphate, Guanosine,Cyclic-3',5'-Monophosphate, Guanosine,GMP, Cyclic,Guanosine Cyclic 3',5' Monophosphate,Monophosphate, Guanosine Cyclic
D006246 Harmaline A beta-carboline alkaloid isolated from seeds of PEGANUM. 3H-Pyrido(3,4-b)indole, 4,9-dihydro-7-methoxy-1-methyl-,Dihydroharmine,Harmidine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014202 Tremor Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of CEREBELLAR DISEASES, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of PARKINSON DISEASE. Action Tremor,Intention Tremor,Resting Tremor,Coarse Tremor,Continuous Tremor,Darkness Tremor,Fine Tremor,Intermittent Tremor,Involuntary Quiver,Massive Tremor,Passive Tremor,Persistent Tremor,Pill Rolling Tremor,Rest Tremor,Saturnine Tremor,Senile Tremor,Static Tremor,Tremor, Limb,Tremor, Muscle,Tremor, Neonatal,Tremor, Nerve,Tremor, Perioral,Tremor, Semirhythmic,Action Tremors,Coarse Tremors,Continuous Tremors,Darkness Tremors,Fine Tremors,Intention Tremors,Intermittent Tremors,Involuntary Quivers,Limb Tremor,Limb Tremors,Massive Tremors,Muscle Tremor,Muscle Tremors,Neonatal Tremor,Neonatal Tremors,Nerve Tremor,Nerve Tremors,Passive Tremors,Perioral Tremor,Perioral Tremors,Persistent Tremors,Pill Rolling Tremors,Quiver, Involuntary,Rest Tremors,Resting Tremors,Saturnine Tremors,Semirhythmic Tremor,Semirhythmic Tremors,Senile Tremors,Static Tremors,Tremor, Action,Tremor, Coarse,Tremor, Continuous,Tremor, Darkness,Tremor, Fine,Tremor, Intention,Tremor, Intermittent,Tremor, Massive,Tremor, Passive,Tremor, Persistent,Tremor, Pill Rolling,Tremor, Rest,Tremor, Resting,Tremor, Saturnine,Tremor, Senile,Tremor, Static,Tremors
D016291 Dizocilpine Maleate A potent noncompetitive antagonist of the NMDA receptor (RECEPTORS, N-METHYL-D-ASPARTATE) used mainly as a research tool. The drug has been considered for the wide variety of neurodegenerative conditions or disorders in which NMDA receptors may play an important role. Its use has been primarily limited to animal and tissue experiments because of its psychotropic effects. Dizocilpine,MK-801,MK 801,MK801

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