5-phenyl-2-furamidines: a new chemical class of potential antidepressants.
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.
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000578:Amidines / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis*; D001763:Blepharoptosis / Q000139:chemically induced; D001921:Brain / Q000378:metabolism; D005663:Furans / Q000138:chemical synthesis / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000378:metabolism; D010095:Oxotremorine / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D012640:Seizures / Q000139:chemically induced; D013574:Synaptosomes / Q000378:metabolism; D013747:Tetrabenazine / Q000037:antagonists & inhibitors; D014202:Tremor / Q000139:chemically induced; D014363:Tryptamines / Q000494:pharmacology
D000578:Amidines; D000928:Antidepressive Agents; D005663:Furans; D018377:Neurotransmitter Agents; D014363:Tryptamines; D010095:Oxotremorine; D000109:Acetylcholine; D013747:Tetrabenazine