Identification of 2-imidazolines as anti-sickling agents.
The drugs tolazoline, clonidine, lofexidine, and fenmetozole were found to inhibit the gelation of hemoglobin S in the order of increasing effectiveness. Only the latter, however, reduced the sickling of red cells significantly and normalized the oxygen affinity of SS blood at 5-10 mM concentrations. Since this level of drug is lower than those reported for many other anti-sickling agents to achieve comparable effects, the 2-imidazoline class of compounds may provide important clues for the development of therapy for sickle cell anemia.
D000755:Anemia, Sickle Cell / Q000097:blood*; D000986:Antisickling Agents; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005782:Gels; D006451:Hemoglobin, Sickle / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007700:Kinetics; D010108:Oxyhemoglobins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014043:Tolazoline / Q000494:pharmacology*
D000986:Antisickling Agents; D005782:Gels; D006451:Hemoglobin, Sickle; D007093:Imidazoles; D010108:Oxyhemoglobins; C029775:oxyhemoglobin S; C010454:fenmetazole; D014043:Tolazoline; D003000:Clonidine; C025655:lofexidine