ABSTRACT
5-[5-(4-Chlorophenyl-2-furanyl)]dihydro-2(3H)-furanone (F-1044), a nonsteroidal antiinflammatory drug related to orpanoxin, lacks the usual acid moiety of such agents. F-1044 had antiinflammatory activity equivalent to ibuprofen's and orpanoxin's in the carrageenin-induced paw edema model in normal and adrenalectomized rats. Antiinflammatory activity was also expressed in the guinea pig UV-induced erythema and rat established arthritis models. F-1044 was a more potent analgesic than ibuprofen and orpanoxin in the rat paw pressure assay. In contrast to the reference agents, F-1044 raised the pain threshold of both the yeast-injected and non-injected paws, suggesting a central component to its analgesic action. F-1044 was more potent than ibuprofen and orpanoxin in the rat brewer's yeast pyresis model. Based on its low activity in inhibiting bradykinin-induced bronchoconstriction in guinea pigs and low gastric irritation activity in rats. F-1044 appears to have a mechanisms of action that involves more than simple inhibition of prostaglandin synthesis. Thus F-1044 is a nonsteroidal antiinflammatory agent with unique chemical and pharmacological features.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Furans/pharmacology , Animals , Arthritis, Experimental/prevention & control , Bronchodilator Agents , Furans/antagonists & inhibitors , Guinea Pigs , Immunosuppressive Agents , Male , Mice , Rats , Rats, Inbred Strains , Stomach Ulcer/chemically induced , Uricosuric AgentsABSTRACT
A series of 5-phenyl-2-furamidines has been synthesized and evaluated for antidepressant activities. Substitution in the phenyl ring with a nitro (4) or an amino (12) group in the ortho-position resulted in an increase in antidepressant activity. Both 4 and 12 antagonized tetrabenazine-induced ptosis in rodents and inhibited norepinephrine (noradrenaline) uptake into crude synaptosomes of whole mouse brain at doses or concentrations comparable to those of the tricyclic antidepressants. However, these compounds did not possess the anticholinergic and antihistaminic activities common to tricyclic antidepressants. In addition, they lacked monoamine oxidase inhibitory activity. The 5-phenyl-2-furamidines represent a new chemical class of antidepressants and may be useful for depressive patients who cannot tolerate the compromising side effects of the tricyclic antidepressants and monoamine oxidase inhibitors.
Subject(s)
Amidines/chemical synthesis , Antidepressive Agents/chemical synthesis , Acetylcholine/antagonists & inhibitors , Amidines/pharmacology , Animals , Blepharoptosis/chemically induced , Brain/metabolism , Furans/chemical synthesis , Furans/pharmacology , Guinea Pigs , In Vitro Techniques , Male , Mice , Muscle Contraction/drug effects , Neurotransmitter Agents/metabolism , Oxotremorine/pharmacology , Rabbits , Rats , Seizures/chemically induced , Synaptosomes/metabolism , Tetrabenazine/antagonists & inhibitors , Tremor/chemically induced , Tryptamines/pharmacologyABSTRACT
The synthesis and antibacterial evaluation of a number of 2-(substituted phenylureido)-4-thiocyanatobenzothiazoles are described. The more active compounds against the test organisms in vitro generally were those substituted with halogens on the phenyl and benzothiazole rings.