Nonpeptide antagonists

Fig. 5 Structures of DOTA-conjugated integrin av/ 3 receptor antagonists (nonpeptides)...

Other potential oxytocia antagonists are being developed using leads from naturally occurring, nonpeptide stmctures, such as an extract from Streptomjces (48). A selective nonpeptide vasopressin receptor antagonist also has been found (49). 

The CCK system shares one property with the opioid system, ie, the existence of selective nonpeptide antagonists. These include aspedicine, a natural benzodiazepine (136), and Devazepide (L-364,718 MK-329) (137). Selective, potent peptide antagonists for CCK, eg, Cl-988 and PD 134308, have been developed that maybe useful as anxiolytics and as dmgs which increase the analgesic effect of morphine but at the same time prevent morphine tolerance (138) (see Hypnotics, sedatives, anticonvulsants, and anxiolytics). 

Fig. 4. Structures of several nonpeptide opioid agonists, (a) morphine, (c) BW373U86, (e) U50488 and antagonists, (b) naloxone, (d) naltrindole, and (f)...

A small-molecule, nonpeptide CCR5 antagonist with highly potent and selective anti-HIV-1 activity. Proc. Natl. AcadSci. USA 96 5698-5703. 

Inhibition of V2 vasopressin receptors causes an increase in urine volume primarily by reducing the re-absoiption of water along the collecting duct, an aquaretic effect that is fundamentally different from the natriuretic actions discussed so far. Nevertheless, some of the conditions calling for the use of natriuretic intervention are identical to those in which the administration of a new class of orally active nonpeptide V2 antagonists may be useful (tolvaptan, lixivaptan, and others). 

Galanin Receptors. Figure 1 Nonpeptide antagonists forGALI (top) and GAL3 (bottom). 

SR 48692 Nonpeptide antagonist at NTS1 agonist at NTS2 Inhibition of tumor growth drug addiction treatment... 

Several nonpeptidic, orally active vasopressin receptor antagonists have been developed. The dual V1A/V2R antagonist conivaptan is used in the treatment of hyponatraemia and could also become useful for diseases such as congestive heart failure, in which increased peripheral resistance and dilutional hyponatremia both are present [4]. Side effects of conivaptan include headache, injection site reactions, vomiting, diarrhoea, constipation and thirst. 

Flohr S, Kurz M, Kostenis E, Brkovich A, Fournier A, Klabunde T. Identification of nonpeptidic urotensin II receptor antagonists by virtual screening based on a pharmacophore model derived from structure-activity relationships and nuclear magnetic resonance studies on urotensin II. J Med Ghent 2002 45 1799-805. 

Junghans U, Siebler M. Cerebral microembohsm is blocked by tirofiban, a selective nonpeptide platelet glycoprotein Ilb/nia receptor antagonist. Circulation 2003 107 2717-2721. 

CCR5 CIA DBA/1 mice A nonpeptide CCR5 antagonist, TAK-779. Also inhibits CXCR3. 

Gao P, Zhou XY, Yashiro-Ohtani Y, et al. The unique target specificity of a nonpeptide chemokine receptor antagonist selective blockade of two Thl chemokine receptors CCR5 and CXCR3. J Leukoc Biol 2003 73(2) 273-280. 

Podolin PL, Bolognese BJ, Foley JJ, et al. A potent and selective nonpeptide antagonist of CXCR2 inhibits acute and chronic models of arthritis in the rabbit. J Immunol 2002 169(ll) 6435-6444. 

Portoghese PS, Sultana M, Nagase H, Takemori AE. Application of the message-address concept in the design of highly potent and selective nonpeptide 6 opioid receptor antagonists. J Med Chem 1988 31 281-282. 

Nonpeptide Antagonists May Bind Rather Differently from the Agonist.103... 

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