P-Receptor antagonists

Picenadol opioid analgesic (-r)-isomer (3.S,4R) p-receptor agonist (-)-isomer (3R.4.5) weak p-receptor antagonist... 

Ethanol also reduces the activity of the noradrenergic system in the locus coeruleus, and alterations in norepinephrine activity may account for some aspects of intoxication and the abstinence syndrome. The 0.2 antagonist clon-idine and the P-receptor antagonist propranolol reduce some symptoms of alcohol withdrawal (Bailly et al. 1992 Carlsson and Fasth 1976 Dobrydnjov et al. 2004 Kahkonen 2003 Petty et al. 1997 Wong et al. 2003). 

Hill, R (2000) NKl (substance P) receptor antagonists—why are they not analgesic in humans Trends Pharmacol. Sci. 21 244 246. 

Herpfer I and Lieb K (2003). Substance P and substance P receptor antagonists in the pathogenesis and treatment of affective disorders. World Journal of Biological Psychiatry, 4, 56-63. 

S. W. Huskey, D. Luffer-Atals, B. J. Dean, E. M. McGowan, W. P. Feeney, S. H. Lee Chiu, Substance P Receptor Antagonist I Conversion of Phosphoramidate Prodrug after i.v. Administration to Rats and Dogs , Drug Metab. Dispos. 1999, 27, 1367- 1373. 

Caesar, M., Seabrook, G. R., Kemp, J. A. Block of voltage-dependent sodium currents by the substance P receptor antagonist CP96.345 in neurones cultured from rat cortex, Br. J. Pharmacol. 1993, 109, 918-924. 

Thereafter, rats were given an injection of the opinoid inhibitor, naloxone, a p,-receptor antagonist, followed by an injection of cetyl-PEG2-enkephalin to demonstrate that... 

Black JW, Crowther AF, Shanks RG, Smith LH, Dornhorst AC. A new adrenergic P-receptor antagonist. Lancet 1964 283 1080-1081. 

Suryanarayana S, Daunt DA, Vonzastrow M, Kobilka BK. A point mutation in the 7th hydrophobic domain of the a2 adrenergic-receptor increases its affinity for a family of P-receptor-antagonists. J Biol Chem 1991 266 15,488-15,492. 

Other p-receptor antagonists have been identified from combinatorial libraries (seebelow). 

In addition to the well known examples of Ilb/IIIa, antagonists of other integrins like a P, (vitronectin receptor), rcP, a pg, fc,P, and a,P have been synthesised. The design of ot p receptor antagonists was based on... 

Af-acylation of L-tryptophan benzyl esters, followed by replacement of the 3,5-dimethyl groups by their trifluor-omethyl analogs, achieved an almost 1,000-fold increase in potency in a series of substance P receptor antagonists (Figure 20.32). ... 

Merchant, K.)., Lewis, R.T., MacLeod, A.M. (1994) Synthesis of homochiral ketones derived from L-tryptophan Potent substance P receptor antagonists. Tetrahedron Lett. 35, 4205 208. 

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