Levamisole is a notoriously unstable molecule, however; breakdown products are apparent within 4 hours in aqueous solutions (in vitro). Conditions that affect the stability of levamisole are pH, light, temperature, and time. The degraded products do not have the same actions as the parent drug. One particular molecule has an inflammatory action that can potentially exacerbate some conditions.
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Multivariate actions of levamisole have consequences in performance horses
Levamisole HCl, originally described for treating helminth infections, is also used for modulating immune responses in humans and animals. Although the mechanisms of actions of levamisole HCl on signal transduction pathways in horses have not been thoroughly defined, levamisole HCl is a cholinergic agonist that causes differential cytokine expression by stimulated leukocytes. Levamisole binds cholinergic receptors found on protozoa, such as those causing Equine Protozoal Myeloencephalitis (EPM).
Serum TNF-α and IL-6 are elevated in acute and chronic infectious or autoimmune inflammatory conditions; when the activity of IL-6 persists after acute inflammation a chronic inflammatory condition can follow. The multivariate actions of levamisole HCl (which include the down regulation of IL6) make it an attractive drug to combat post-treatment neuroinflammation seen in Lyme disease and Equine Protozoal Myeloencephalitis (EPM) in horses.
One should know the actions of drug combinations that contain levamisole before administering them to horses.
Levamisole is used ubiquitously in horse products. Recently levamisole was found in some compounded paste formulations (Toltrazuril/pyrimethamine Oral Paste, BRD) that did not list the substance on the label.
In vivo assays in horses show that levamisole (with a half-life of 1 to 4 hours) is metabolized rather quickly. The elimination of by-products in the serum associated with the metabolism of levamisole HCl, however, can take much longer. Some by-products are detectable in the plasma for longer than 70 hours. Pemoline, a putative levamisole-induced endogenous molecule, has a half-life of 6.5 days.
Levamisole is classified by the Association of Racing Commissioners (ARC) International’s Uniform Classification Guidelines as a Class 2, Penalty Class B substance. Because there are fines and penalties corresponding to the administration of levamisole to competition horses it is important that reporting laboratories are uniform in identification and detection of this substance and publish safe withdrawal times.
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