[Montirelin hydrate (NS-3), a TRH analog, improved the disturbance of consciousness caused by head concussion and pentobarbital in mice]. 1996

T Mushiroi, and R Shibahara, and M Tamura, and T Shimizu, and Y Itoh, and Y Ukai, and Y Yoshikuni, and K Kimura
Research Laboratories, Nippon Shinyaku Co. Ltd., Kyoto, Japan.

Effects of a novel TRH analog, montirelin hydrate (NS-3), on the coma caused by head concussion and narcosis induced by pentobarbital were compared with those of TRH in mice. Head concussion caused a behavioral comatose state with loss of the righting reflex and spontaneous motor activity. NS-3 shortened the latent periods to the recovery of the righting reflex (0.03-0.1 mg/kg, i.v.) and spontaneous motor activity (0.1 mg/kg, i.v.) following the head concussion. In the case of TRH, higher doses were needed to induce such effects. NS-3 (0.1-0.3 mg/kg, i.v.) reversed the pentobarbital-induced narcosis in a dose-dependent manner. A similar effect was elicited by 30- to 100-fold higher doses of TRH than NS-3. The analeptic effect of NS-3 in the pentobarbital-narcotized mice was antagonized by SCH23390, a dopamine D1 antagonist or by the combined treatment with prazosin and scopolamine, while neither prazosin nor scopolamine alone antagonized the analeptic effect of NS-3. Taken together with the finding that NS-3 did not bind to dopamine, adrenaline or muscarine receptors, it is suggested that NS-3 may restore the disturbance of consciousness by activating the brain dopamine, noradrenaline and acetylcholine neurons without stimulating these receptors directly.

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
D011957 Receptors, Opioid Cell membrane proteins that bind opioids and trigger intracellular changes which influence the behavior of cells. The endogenous ligands for opioid receptors in mammals include three families of peptides, the enkephalins, endorphins, and dynorphins. The receptor classes include mu, delta, and kappa receptors. Sigma receptors bind several psychoactive substances, including certain opioids, but their endogenous ligands are not known. Endorphin Receptors,Enkephalin Receptors,Narcotic Receptors,Opioid Receptors,Receptors, Endorphin,Receptors, Enkephalin,Receptors, Narcotic,Receptors, Opiate,Endorphin Receptor,Enkephalin Receptor,Normorphine Receptors,Opiate Receptor,Opiate Receptors,Opioid Receptor,Receptors, Normorphine,Receptors, beta-Endorphin,beta-Endorphin Receptor,Receptor, Endorphin,Receptor, Enkephalin,Receptor, Opiate,Receptor, Opioid,Receptor, beta-Endorphin,Receptors, beta Endorphin,beta Endorphin Receptor,beta-Endorphin Receptors
D011976 Receptors, Muscarinic One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for MUSCARINE over NICOTINE. There are several subtypes (usually M1, M2, M3....) that are characterized by their cellular actions, pharmacology, and molecular biology. Muscarinic Acetylcholine Receptors,Muscarinic Receptors,Muscarinic Acetylcholine Receptor,Muscarinic Receptor,Acetylcholine Receptor, Muscarinic,Acetylcholine Receptors, Muscarinic,Receptor, Muscarinic,Receptor, Muscarinic Acetylcholine,Receptors, Muscarinic Acetylcholine
D001924 Brain Concussion A nonspecific term used to describe transient alterations or loss of consciousness following closed head injuries. The duration of UNCONSCIOUSNESS generally lasts a few seconds, but may persist for several hours. Concussions may be classified as mild, intermediate, and severe. Prolonged periods of unconsciousness (often defined as greater than 6 hours in duration) may be referred to as post-traumatic coma (COMA, POST-HEAD INJURY). (From Rowland, Merritt's Textbook of Neurology, 9th ed, p418) Cerebral Concussion,Commotio Cerebri,Concussion, Intermediate,Concussion, Mild,Concussion, Severe,Mild Traumatic Brain Injury,Brain Concussions,Cerebral Concussions,Concussion, Brain,Concussion, Cerebral,Intermediate Concussion,Intermediate Concussions,Mild Concussion,Mild Concussions,Severe Concussion,Severe Concussions
D003244 Consciousness Disorders Organic mental disorders in which there is impairment of the ability to maintain awareness of self and environment and to respond to environmental stimuli. Dysfunction of the cerebral hemispheres or brain stem RETICULAR FORMATION may result in this condition. Consciousness, Level Altered,Disorder of Consciousness,Disorders of Consciousness,Semiconsciousness,Altered Level of Consciousness,Consciousness, Level Depressed,Depressed Level of Consciousness,Consciousness Disorder
D000758 Anesthesia A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures.
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
D013973 Thyrotropin-Releasing Hormone A tripeptide that stimulates the release of THYROTROPIN and PROLACTIN. It is synthesized by the neurons in the PARAVENTRICULAR NUCLEUS of the HYPOTHALAMUS. After being released into the pituitary portal circulation, TRH (was called TRF) stimulates the release of TSH and PRL from the ANTERIOR PITUITARY GLAND. Protirelin,Thyroliberin,Abbott-38579,Antepan,Proterelin Tartrate,Proterelin Tartrate Hydrate,Protirelin Tartrate (1:1),Relefact TRH,Stimu-TSH,TRH Ferring,TRH Prem,Thypinone,Thyroliberin TRH Merck,Thyrotropin-Releasing Factor,Thyrotropin-Releasing Hormone Tartrate,Abbott 38579,Abbott38579,Hydrate, Proterelin Tartrate,Prem, TRH,Stimu TSH,StimuTSH,TRH, Relefact,Tartrate Hydrate, Proterelin,Thyrotropin Releasing Factor,Thyrotropin Releasing Hormone,Thyrotropin Releasing Hormone Tartrate

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