[General pharmacological studies on human natural tumor necrosis factor (MHR-24)].
The general pharmacological properties of MHR-24 were studied in various experimental animals. Intravenously (i.v.)-administered MHR-24 at 8.6 x 10(2) JRU/kg or more produced fever in rabbits. MHR-24 at 3 x 10(4) JRU/kg or more caused tachycardia; and at 1 x 10(5) JRU/kg or more, it lowered arterial blood pressure in anesthetized monkeys. In rats, MHR-24 at 2.9 x 10(4) JRU/kg or more showed a diuretic action and inhibitory effects on gastric juice secretion and carrageenin-induced paw edema. Furthermore, MHR-24 at a large dose (8.6 x 10(4) or 2.9 x 10(5) JRU/kg, i.v.) decreased spontaneous locomotor activity, had an inhibitory effect on acetic acid-induced writhing and potentiated intestinal propulsion in mice; and it caused the appearance of rest wave on acute spontaneous electroencephalograms in rabbits. Pretreatment of the animals with the cyclooxygenase inhibitor indomethacin abolished the fever and potentiation of intestinal propulsion caused by MHR-24. Therefore, these data seem to indicate that some of the effects of MHR-24 are mediated via cyclooxygenase pathways. The results suggested that, except for the above results, MHR-24 has no noticeable effects on the central nervous, autonomic nervous, respiratory and cardiovascular systems and others in general pharmacological studies.
Sato
M
M
Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd., Gotemba, Japan.
Imada
K
K
Iida
S
S
Ohashi
K
K
Kimura
S
S
Niho
T
T
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002415:Cats; D004232:Diuretics / Q000494:pharmacology; D005260:Female; D005750:Gastric Juice / Q000378:metabolism; D005769:Gastrointestinal Motility / Q000187:drug effects; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D004232:Diuretics; D014409:Tumor Necrosis Factor-alpha; D007213:Indomethacin