Levodropropizine reduces capsaicin- and substance P-induced plasma extravasation in the rat trachea.
We investigated the effect of the non-opioid, peripherally acting antitussive agent levodropropizine to reduce neurogenic plasma extravasation in the rat trachea. Levodropropizine (10, 50 and 200 mg/kg) reduced in a dose-dependent manner the extravasation of Evans blue dye evoked by capsaicin. Levodropropizine inhibited also substance P-evoked extravasation, whereas it did not affect the extravasation evoked by platelet activating factor. Levodropropizine (10 and 100 microM) did not affect the contraction produced by [Sar9,Met(O2)11]substance P, a selective agonist for tachykinin NK1 receptors, in the rat urinary bladder in vitro. These data indicate that levodropropizine inhibits capsaicin-induced plasma extravasation: (a) acting at a postjunctional level; (b) exhibiting neuropeptide selectivity and; (c) via a mechanism independent of tachykinin NK1 receptor blockade. Irrespective of the mechanism, this novel antiinflammatory action of levodropropizine underlines its potential role in inflammatory airway diseases such as bronchial asthma.
Yamawaki
I
I
Cardiovascular Research Institute, University of California, San Francisco 94143-0130.
Geppetti
P
P
Bertrand
C
C
Huber
O
O
Daffonchio
L
L
Omini
C
C
Nadel
J A
JA
D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005070:Evans Blue; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000097:blood*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D017933:Peripheral Nervous System / Q000187:drug effects; D010972:Platelet Activating Factor / Q000494:pharmacology; D011409:Propylene Glycols / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology*; D014132:Trachea / Q000098:blood supply* / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects
D000996:Antitussive Agents; D010972:Platelet Activating Factor; D011409:Propylene Glycols; C062618:substance P, Sar(9)-Met(O2)(11)-; D013373:Substance P; D005070:Evans Blue; D002211:Capsaicin; C035916:dipropizine