Characterization of Spinal Actions of Ten Substance P Analogs

On the basis of data obtained in smooth muscles [1] it was assumed that substance P (SP) analogues containing D-amino acids will antagonise the spinal actions of tachykinins. It was however rapidly realised that SP antagonists exert direct effects on the rat spinal cord. In fact, undeca or C-terminal octapeptide analogues of SP containing D-Trp in positions 7 and 9 or 7,9 and 10 cause an initial increase of the blood pressure followed by a long lasting fall to levels below 80 mmHg within 20–30 min when applied intrathecally (i.th.). In a number of experiments, the hypotension was large enough to cause death of the animal [2, 3, 4].