Melanocortin receptor agonists

Formerly known as PT-141 from Palatin Technologies is in phase 2 clinical trials. It is a melanocortin receptor agonist and is being trialled for male and female sexual dysfunction and is believed to have none of the cardiovascular effects possibly associated with other therapies. 

Bellasio S, Nicolussi E, Bertorelli R, Reggiani A (2003) Melanocortin receptor agonists and antagonists modulate nociceptive sensitivity in the mouse formalin test. Eur J Pharmacol 482 127-132... 

Figure 2.6. Structure of the potent nonselec-tive human melanocortin receptor agonist MT-II.

Melanotan II or PT-141 (Palatin Technologies) is a synthetic analog of melanocyte-stimulating hormone (161). The peptide is currently under development as an intranasal formulation for both male and female sexual dysfunction. It is a non-selective melanocortin receptor agonist, which in animals regulates sexual behavior including penile erection, sexual motivation, and in female rats, the secre-... 

Toda, C., T. Shiuchi, S. Lee, M. Yamato-Esaki, Y. Fujino, A. Suzuki, S. Okamoto, and Y. Minokoshi, 2009. Distinct effects of leptin and a melanocortin receptor agonist injected into medial hypothalamic nuclei on glucose uptake in peripheral tissues. Diabetes. 58(12), 2757-2765. 

Abdel-Malek ZA (2001) Melanocortin receptors their functions and regulation by physiological agonists and antagonists. Cell Mol Life Sci 58 434 141... 

Nargund, R.P., Ye, Z., Palucki, B., Bakshi, R., Patchett, A.A. and Van der Ploeg, L.H. (1999) WO 99/64002. Novel spiropiperidine derivatives with melanocortin-4-receptor agonist activity. Assigned to Merck, Sharp and Dohme Ltd. 

Ujjainwalla F, Chu L, Goulet MT, Lee B, Warner D, Wyvratt MJ, inventors Merck Co. Inc., assignee. Acylated piperidine derivatives as melanocortin-4 receptor agonists. WO/ 2002/068388,2002 Sep 06. 

Diaryl-5-anilino-l,2,4-thiadiazoles are found to be potent and selective melanocortin-4-receptor (MC4) agonists for potential use for nerve regeneration and drug addiction <2003BMG185>. Compounds like 56 are being developed as cysteine protease inhibitors (see also Section 5.07.10) <2005JOC6230>. 

Herpin TF, Yu G, Carlson KE, et al. Discovery of tyrosine-based potent and selective melanocortin-1 receptor small-molecule agonists with anti-inflammatory properties, / Med Chem 2003 46 1123-26. 

Richardson TI, Qmstein PL, Briner K, et al. Synthesis and structure-activity relationships of novel arylpiperazines as potent and selective agonists of the melanocortin subtype-4 receptor. / Med Chem 2004 47 744-55. 

Serotonin. Serotonin central receptors appear to play a major role in glucose homeostasis. Experiments in obese mice have demonstrated that small doses of a classical serotonin agonist, metachlorophenylpiperazine (mCPP), markedly lower plasma insulin levels and increase insulin sensitivity, without affecting food intake, body weight or fat mass. The downstream target of the involved serotonin receptor appears to be melanocortin-4 receptors, in the arcuate nucleus of the hypothalamus. 

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