Inhalation of substance P and thiorphan: acute toxicity and effects on respiration in conscious guinea pigs.
Substance P is a tachykinin and a biologically active neuropeptide. The peptide produces salivation, neuronal excitation, vasodilatation, increased vascular permeability and contraction of smooth muscles in the respiratory tract. The study was designed to evaluate the acute effects in guinea pigs of inhaled aerosolized Substance P (SP). Apart from the acute toxic effect of the peptide, the distribution in different organs was also investigated. The acute inhalation toxicity of SP (LC50, 15 min) when co-administrated with the neutral endopeptidase inhibitor thiorphan was 368 microg m(-3). The peptide caused an increase in respiratory rate proceeding a decrease in tidal volume. As the exposure proceeded, a decrease in both respiratory rate and further decreases in tidal volume were observed until either the animal died or the exposure was terminated. The decreases in respiratory rate and tidal volume were probably due to bronchoconstriction caused by SP. Eighteen per cent of the inhaled amount of radioactive SP was retained in the body, and the highest concentrations of radioactivity were found in the kidney, lung and liver. Substance P in combination with thiorphan administered as an aerosol is extremely toxic and highly potent. Exposure to the substance at extremely low air concentrations may result in incapacitation in humans.
Koch
B L
BL
Defence Research Establishment, Department of Biomedicine, Umeå, Sweden. koch@ume.foa.se
Edvinsson
A A
AA
Koskinen
L O
LO
D000280:Administration, Inhalation; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006168:Guinea Pigs; D008171:Lung Diseases / Q000139:chemically induced*; D008297:Male; D011480:Protease Inhibitors / Q000633:toxicity*; D012119:Respiration / Q000187:drug effects*; D013373:Substance P / Q000633:toxicity*; D015996:Survival Rate; D015244:Thiorphan / Q000493:pharmacokinetics / Q000633:toxicity*; D013990:Tidal Volume / Q000187:drug effects; D013997:Time Factors