Anti-asthmatic activity of newly synthesized calcium antagonists: 2-n-butyl-1 (N-methyl-n-[2-(N',N'-dimethylamino)ethyl]amino) -5,6-methylenedioxy-indene and -indane.
The anti-asthmatic activity of the newly synthesized methylenedioxyindene (MDI) derivatives, 2-n-butyl-1 (N-methyl-N-[2-(N', N' -dimethylamino)ethyl]amino)-5, 6-methylenedioxy-indene (MDI-C) and -indane (MDI-D), were investigated in vitro and in vivo in guinea pigs. The in vitro pharmacological activity of both derivatives was compared to that of 8-(diethylamino)octyl-3,4, 5-trimethyoxybezoate hydrochloride. All three agents caused a concentration-dependent inhibition of the antigen-induced contraction of sensitized guinea pig tracheal smooth muscle. In histamine and leukotriene D4-induced contractions of guinea pig tracheal smooth muscle, each agent showed clear antagonistic actions. Additionally, all three agents demonstrated potent calcium antagonistic actions via inhibition of guinea pig tracheal smooth muscle contractions caused by CaCl2 in a high potassium and Ca-free medium and by compound 48/80 in a solution of ethylene glycol bis(beta-aminoethylether)-N,N,N',N'-tetraacetic acid in a contained Ca-free medium. MDI-C and MDI-D inhibited the antigen-induced release of histamine and slow reacting substance of anaphylaxis from sensitized guinea pig lung tissue. Lastly, both MDI is clearly inhibited asthmatic respiratory disorders without affecting blood pressure in guinea pigs.
Nagai
H
H
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Yakuo
I
I
Arimura
A
A
Choi
S H
SH
Inagaki
N
N
Koda
A
A
D000818:Animals; D001249:Asthma / Q000188:drug therapy*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007189:Indans / Q000494:pharmacology*; D007192:Indenes / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D013189:SRS-A / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000502:physiology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007189:Indans; D007192:Indenes; D013189:SRS-A; C060698:2-butyl-1-(N-methyl-N-(2-(N',N'-dimethylamino)ethyl)amino)-5,6-methylenedioxyindene; C061797:2-(n-butyl)-1-(N-methyl-N-(2-(N',N'-dimethylamino)ethyl)amino)-5,6-methylenedioxyindane; D003189:p-Methoxy-N-methylphenethylamine; D006632:Histamine; D002118:Calcium