General pharmacology of [2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3- dihydro-1H-pyrrolizine-5-yl]-acetic acid in experimental animals.
[2,2-Dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine-5- yl]-acetic acid (ML 3000) is a newly synthesized compound with analgesic, antipyretic and anti-inflammatory activity. The general pharmacological effects of ML 3000 following oral administration were investigated in experimental animals. The results showed that with regard to the CNS, ML 3000 did not affect behaviour in the Irwin test, locomotor activity or hexobarbital-induced sleep at doses of 30, 100 and 300 mg/kg. ML 3000, at a single dose of 100 mg/kg administered intraduodenally, had no notable effect on the cardiovascular system or respiration in anaesthestised rats and dogs nor on neuromuscular function in anaesthetised cats. No evidence of gastric damage or disturbance of peristalsis was observed following oral administration of ML 3000. In vitro, ML 3000 evoked a weak spasmogenic response in the guinea-pig ileum with a dose-related inhibition of acetylcholine, histamine and barium chloride-induced responses. A small transient reduction in urine volume was observed after the highest dose accompanied by decreases in electrolyte excretion at doses of 100 and 300 mg/kg in rats. The results demonstrate that ML 3000 has no notable general pharmacological effects under the experimental conditions reported.
Algate
D R
DR
Department of Pharmacology, Huntingdon Research Centre, UK.
Augustin
J
J
Atterson
P R
PR
Beard
D J
DJ
Jobling
C M
CM
Laufer
S
S
Munt
P L
PL
Tries
S
S
D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002415:Cats; D002490:Central Nervous System / Q000187:drug effects; D004064:Digestive System / Q000187:drug effects; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012137:Respiratory System / Q000187:drug effects
D000085:Acetates; D016859:Lipoxygenase Inhibitors; D011758:Pyrroles; C088092:licofelone