New pharmacological aspects on the antiasthmatic activity of tiaramide-HCl.
Tiaramide hydrochloride (THC) is a benzothiazoline derivative with a remarkable antianaphylactic activity: in anaesthetized guinea-pig it shows protecting effects against histamine (H)- and bradykinin (Bk)-induced bronchoconstriction, preventing increase of lung resistance and decrease of dynamic compliance. At the same time THC inhibits formation of circulating thromboxane A2 brought about by H and Bk. THC is also able to antagonize the contractions induced by CaCl2 on isolated guinea-pig tracheal spirals and its mode of action seems to be of the competitive type. Furthermore THC abolishes the "tonic" phase of K+-induced contractions of guinea-pig taenia coli which are dependent on inward movement of calcium, whereas the "phasic" component of the contractions is left unaltered. THC is a very weak inhibitor of 3'-5' cyclic adenosine monophosphate phosphodiesterase which is affected only at very high dosage (10(-2) M). The calcium antagonistic activity of THC may explain both its bronchodilating and antianaphylactic properties.
D000707:Anaphylaxis / Q000503:physiopathology; D000818:Animals; D001249:Asthma / Q000188:drug therapy*; D052160:Benzothiazoles; D001980:Bronchi / Q000187:drug effects; D001986:Bronchial Spasm / Q000188:drug therapy; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers; D002462:Cell Membrane / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism
D052160:Benzothiazoles; D002121:Calcium Channel Blockers; D010879:Piperazines; C003468:tiaramide; D011188:Potassium; D002118:Calcium