High-performance liquid chromatographic determination of (Me)Arg-Lys-Pro-Trp-tert.-Leu-Leu in plasma

Machida, Ryouichi; Tokumura, Tadakazu; Sasaki, Atsushi; Tsuchiya, Yutaka; Abe, Kouichi

doi:10.1016/s0378-4347(00)82161-1

Cited by 11 publications

(1 citation statement)

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“…Thus, peptide NT1 or "Eisai peptide", [24][25][26] a modified analogue of NT (8)(9)(10)(11)(12)(13), was the first agonist able to induce biological activity, such as analgesia, hypothermia, and hypolocomotion, after systemic administration in animals. 27,28 More recently, the group of Richelson was interested in peptidaseresistant NT agonists able to cross the blood-brain barrier and presenting high binding affinity for the NTS1 receptor.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Effects of c(Lys-Lys-Pro-Tyr-Ile-Leu-Lys-Lys-Pro-Tyr-Ile-Leu) (JMV2012), a New Analogue of Neurotensin that Crosses the Blood−Brain Barrier

et al. 2008

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The central administration of neurotensin (NT) or of its C-terminal hexapeptide fragment NT(8-13), produces strong analgesic effects in tests evaluating acute pain. The use of NT-derived peptides as pharmaceutical agents to relief severe pain in patients could be of great interest. Unfortunately, peptides do not readily penetrate the blood-brain barrier. We have observed that the cyclic NT(8-13) analogue, c(Lys-Lys-Pro-Tyr-Ile-Leu-Lys-Lys-Pro-Tyr-Ile-Leu) (JMV2012, compound 1), when peripherally administered to mice produced analgesic and hypothermic effects, suggesting the peptide penetrates the blood-brain barrier and functions effectively like a drug. Moreover, dimeric compounds show increased potency compared to their corresponding monomer. We present the synthesis of the cyclic dimer compound 1 (JMV2012). In mice, compound 1 induced a profound hypothermia and a potent analgesia, even when peripherally administered. Compound 1 appears to be an ideal lead compound for the development of bioactive NT analogues as novel analgesics drugs.

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