Differential antagonism

Miczek, K.A. Differential antagonism of (f-amphetamine effects on motor activity and agonistic behavior in mice. Soc Neurosci Abstr 7 343, 1981a. 

Miczek, K.A., and Yoshimura, H. Disruption of primate social behavior by (/-amphetamine and cocaine Differential antagonism by antipsychotics. Psychopharmacology 76 163-171, 1982. 

Sofuoglu M, Portoghese P, Takemori A. Differential antagonism of delta opioid agonists by naltrindole and its benzofuran analog (NTB) in mice evidence for delta opioid receptor subtypes. 

Wilding, T. J. and Huettner, J. E. (1995) Differential antagonism of alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid-preferring and kainate-preferring receptors by 2,3-benzodiazepines. Mol. Pharmacol. 47, 582-587. 

Rosecrans. J. A., Young, R., and Glennon, R. A. (1983) Differential antagonism of the 5-methoxy-N,N-dimethyltryptamine stimulus by various serotonin antagonists. Pharmacol. Biochem. Behav. (submitted for publication). 

Jiang, Q., Takemori, A.E., Sultana, M., etal. Differential antagonism of opioid delta antinociception by [D-Ala2,Leu5,Cys6]enkephalin and naltrindole 5 -isothiocyanate evidence for delta receptor subtypes, J. Pharmacol. Exp.Ther. 1991, 257, 1069-1095. 

Sakurada S, Hayashi T, Yuhki M, Fujimura T, Murayama K, Yonezawa A, Sakurada C, Takeshita M, Zadina JE, Kastin AJ, Sakurada T (2000) Differential antagonism of endomorphin-1 and endomorphin-2 spinal nociception by naloxonazine and 3-methoxynaltraxone. Brain Res 881 1-8... 

Pauwels PJ, Rauly I, Wurch T. Dissimilar pharmacological responses by a new series of imidazoline derivatives at precoupled and ligand-activated a2A-adreno-ceptor states Evidence for effector pathway-dependent differential antagonism. J Pharmacol Exp Ther 2003 305 1015-1023. 

Other specific discovery assays have been used such as differential inhibition of a vancomycin resistant S. aureus strain and its susceptible parent, and an assay based on antagonism of the antibacterial activity by N,A/-diacetyl-L-Lys-D-Ala-D-Ala [24570-39-6] a tripeptide analogue of the dalbaheptides receptor. AppHcation of this latter test to 1936 cultures (90) led to the isolation of 42 dalbaheptides, six of which, including kibdelin (Table 3), parvodicin (Table 3), and actinoidin A2 (68) were novel. A colorimetric assay based on competition between horseradish peroxidase bound teicoplanin and the... 

Most recently, a phase-I-study defined a dose of 13-ris-retinoic acid that was tolerable in patients after myeloablative therapy, and a phase-III-trial showed that postconsolidation therapy with 13-cis-retinoic acid improved EFS for patients with high-risk neuroblastoma [7]. Preclinical studies in neuroblastoma indicate that ATRA or 13-cw-RA can antagonize cytotoxic chemotherapy and radiation, such that use of 13-cis-RA in neuroblastoma is limited to maintenance after completion of cytotoxic chemotherapy and radiation. It is likely that recurrent disease seen during or after 13-cis-RA therapy in neuroblastoma is due to tumor cell resistance to retinoid-mediated differentiation induction. Studies in neuroblastoma cell lines resistant to 13-cw-RA and ATRA have shown that they can be sensitive, and in some cases collaterally hypersensitive, to the cytotoxic retinoid fenretinide. Here, fenretinide induces tumor cell cytotoxicity rather than differentiation, acts independently from RA receptors, and in initial phase-I-trials has been well tolerated. Clinical trials of fenretinide, alone and in combination with ceramide modulators, are in development. 

Despite these problems it remains necessary to attempt some explanation in terms of differential NT antagonism, of why clozapine is so effective (see Reynolds 1997) in that it causes fewer EPSs, reduces negative symptoms and is effective in some patients refractory to other drugs. Considering these benefits in turn ... 

Sleep and sedative effects of the atypical antipsychotics could be related to different mechanisms antagonism of 5-HT2 receptors, antihistaminic and antimus-carinic effects, and probably an a-1 noradrenergic effect. The difference in the effect on sleep between risperidone and haloperidol may be due to their differential actions on serotoninergic receptors (Trampus and Ongini 1990 Trampus et al. 1993). 

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