5/6/7/8 mono or disubstituted 1H/1-phenyl-9H-pyrido [3,4 b] indoles--a new class of antifilarial agents and their relationship with voltage sensitive calcium channels in Setaria cervi.
Synthetic compounds of 5/6/7/8 mono or disubstituted 1H/1-phenyl-9H pyrido (3,4 b) indole series were screened for their antifilarial activity in vitro by observing their effect on the spontaneous movements of the whole worm and nerve muscle preparation of S. cervi (Nematoda:Filarioidea). Of the 10 compounds tested only compound 87/581 was able to modify the movements of whole worm and nerve muscle preparation. This compound caused inhibition of spontaneous motility of whole worm and nerve muscle preparation of S. cervi characterized by initial short lasting stimulation followed by irreversible paralysis. The concentration required to inhibit the movements of n.m. preparation was 10 micrograms/ml as compared to 25 micrograms/ml for the whole worm preparation, suggesting a cuticular permeability barrier. Prior addition of compound 87/581 to the bath fluid blocked the calcium ion dependent stimulant effect of Ach and pyrantel pamoate. Further the initial stimulant effect of the compound was blocked by prior addition of nifedipine a calcium channel blocker. The findings suggest that the action is due to blockade of voltage sensitive calcium channels.
Kapoor
S
S
Department of Pharmacology, J.N. Medical College, Aligarh Muslim University, India.
Singhal
K C
KC
D000818:Animals; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D005369:Filaricides / Q000737:chemistry / Q000145:classification / Q000494:pharmacology*; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology; D017182:Setaria Nematode / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D005369:Filaricides; D007211:Indoles; D009543:Nifedipine