Wiese AJ, Rathbun M, Butt MT, Malkmus SA, Richter PJ, Osborn KG, Xu Q, Veesart SL, Steinauer JJ, Higgins D, Lappi DA, Russell B, Yaksh TL (2013) Intrathecal substance p-saporin in the dog: distribution, safety, and spinal neurokinin-1 receptor ablation. Anesthesiology 119(5):1163-1177. doi: 10.1097/ALN.0b013e3182a95164
Summary: Here the authors investigate the safety parameters of SP-SAP on purpose-bred beagles (currently in human clinical trials). The dogs received 1.5, 15, or 150 μg intrathecal injections of the conjugate. SP-SAP pharmacology and physiological effects were assessed by behavioral and functional observations, immunohistochemistry, ELISA, blood and urine analysis, histopathology, and in situ hybridization. The general conclusions include that neurokinin-1 receptor (NK1r) positive neuron loss is detectable as soon as 7 days after administration of SP-SAP, the neuron loss is permanent, toxicity is specific to NK1r-positive neurons, and, other than the 150 μg dose, NK1r neuron loss was restricted to the superficial dorsal horn.