Biomaterial Database

Proglumide, a cholecystokinin receptor antagonist, exacerbates beta, beta'-iminodipropionitrile-induced dyskinetic syndrome in rats. 1998

M Tariq, and H A Khan, and Z Rehana, and K Al Moutaery, and S Al Deeb

Neuroscience Research Group, Armed Forces Hospital, Riyadh, Saudi Arabia.

The present investigation was undertaken to study the effect of proglumide, a cholecystokinin (CCK) receptor antagonist, on iminodipropionitrile (IDPN)-induced excitation, chorea, and circling (ECC) syndrome in rats. The animals were exposed to IDPN in the dose of 100 mg/kg/day IP for 9 days. Proglumide (PG) was administered IP daily 1 h before IDPN in the doses of 250, 500, and 750 mg/kg body weight in three different groups of rats. The animals were observed daily for neurobehavioral abnormalities including dyskinetic head movements, circling, tail hanging, air righting reflex, locomotor activity, and contact inhibition of the righting reflex. After behavioral studies, blood and brain samples were collected for the analysis of malondialdehyde (MDA), conjugated dienes, vitamin E, and glutathione peroxidase (GSH-Px). The temporal bones were also collected for inner ear histopathology. Our results showed that proglumide significantly and dose-dependently exacerbated the incidence and the severity of IDPN-induced ECC syndrome during the treatment period as well as up to 3 weeks of postdosing. Administration of IDPN produced a significant increase in MDA and conjugated dienes and a decrease in vitamin E and GSH-Px, suggesting the role of oxygen-derived free radicals (ODFR) in IDPN-induced neurotoxicity. Concomitant treatment with proglumide potentiated IDPN-induced oxidative stress. The histopathology of the inner ear showed significantly high degeneration of sensory hair cells in the crista ampullaris of the rats treated with IDPN plus proglumide compared to IDPN-alone-treated animals. Further studies are warranted to determine the role of CCK in nitrile toxicity and drug-induced dyskinesia.

UI	MeSH Term	Description	Entries
D007758	Ear, Inner	The essential part of the hearing organ consists of two labyrinthine compartments: the bony labyrinthine and the membranous labyrinth. The bony labyrinth is a complex of three interconnecting cavities or spaces (COCHLEA; VESTIBULAR LABYRINTH; and SEMICIRCULAR CANALS) in the TEMPORAL BONE. Within the bony labyrinth lies the membranous labyrinth which is a complex of sacs and tubules (COCHLEAR DUCT; SACCULE AND UTRICLE; and SEMICIRCULAR DUCTS) forming a continuous space enclosed by EPITHELIUM and connective tissue. These spaces are filled with LABYRINTHINE FLUIDS of various compositions.	Labyrinth,Bony Labyrinth,Ear, Internal,Inner Ear,Membranous Labyrinth,Bony Labyrinths,Ears, Inner,Ears, Internal,Inner Ears,Internal Ear,Internal Ears,Labyrinth, Bony,Labyrinth, Membranous,Labyrinths,Labyrinths, Bony,Labyrinths, Membranous,Membranous Labyrinths
D008297	Male		Males
D009043	Motor Activity	Body movements of a human or an animal as a behavioral phenomenon.	Activities, Motor,Activity, Motor,Motor Activities
D009498	Neurotoxins	Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept.	Alpha-Neurotoxin,Excitatory Neurotoxin,Excitotoxins,Myotoxin,Myotoxins,Neurotoxin,Alpha-Neurotoxins,Excitatory Neurotoxins,Excitotoxin,Alpha Neurotoxin,Alpha Neurotoxins,Neurotoxin, Excitatory,Neurotoxins, Excitatory
D009570	Nitriles	Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.	Nitrile
D011377	Proglumide	A drug that exerts an inhibitory effect on gastric secretion and reduces gastrointestinal motility. It is used clinically in the drug therapy of gastrointestinal ulcers.	Xylamide,Milid,Xilamide
D011949	Receptors, Cholecystokinin	Cell surface proteins that bind cholecystokinin (CCK) with high affinity and trigger intracellular changes influencing the behavior of cells. Cholecystokinin receptors are activated by GASTRIN as well as by CCK-4; CCK-8; and CCK-33. Activation of these receptors evokes secretion of AMYLASE by pancreatic acinar cells, acid and PEPSIN by stomach mucosal cells, and contraction of the PYLORUS and GALLBLADDER. The role of the widespread CCK receptors in the central nervous system is not well understood.	CCK Receptors,Caerulein Receptors,Cholecystokinin Octapeptide Receptors,Cholecystokinin Receptors,Pancreozymin Receptors,Receptors, CCK,Receptors, Caerulein,Receptors, Pancreozymin,Receptors, Sincalide,Sincalide Receptors,CCK Receptor,CCK-4 Receptors,CCK-8 Receptors,Cholecystokinin Receptor,Receptors, CCK-4,Receptors, CCK-8,Receptors, Cholecystokinin Octapeptide,CCK 4 Receptors,CCK 8 Receptors,Octapeptide Receptors, Cholecystokinin,Receptor, CCK,Receptor, Cholecystokinin,Receptors, CCK 4,Receptors, CCK 8
D001835	Body Weight	The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.	Body Weights,Weight, Body,Weights, Body
D004357	Drug Synergism	The action of a drug in promoting or enhancing the effectiveness of another drug.	Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D004409	Dyskinesia, Drug-Induced	Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)	Dyskinesia, Medication-Induced,Medication-Induced Dyskinesia,Drug-Induced Dyskinesia,Drug-Induced Dyskinesias,Dyskinesia, Drug Induced,Dyskinesia, Medication Induced,Dyskinesias, Drug-Induced,Dyskinesias, Medication-Induced,Medication Induced Dyskinesia,Medication-Induced Dyskinesias