K-Receptor agonists

Butorphanol is a synthetic 14-hydroxymorphinan analogue with a low dependence potential and a low propensity to cause opioid adverse effects (1). It is a synthetic OP2 (k) receptor agonist and OP3 ( ) receptor antagonist. 

Fentanyl is a jl receptor agonist that significantly increases locomotor activity in horses (0.02 mg/kg). Addition of a specific k receptor agonist (U50,488H) to fentanyl enhanced the loco-motory effect, with a more rapid onset and longer duration. This may indicate that locomotor activity is mediated by both jjl and k receptors or it may be the result of altered pharmacokinetics of fentanyl in the presence of the second drug (Mama et al 1993). Fentanyl (0.01-0.05 mg/kg i.v.) caused marked inhibition of propulsive activity in the equine colon with closure of the cecocolic sphincter that lasted for 60-120 min (Roger et al 1994). 

Butorphanol is the opioid agonist-antagonist that is most frequently used in the horse. It is a K receptor agonist and can antagonize the effect of JL agonists at the x opioid receptor (Sellon et al 2001). Butorphanol is used in combination with another sedative for standing chemical restraint and as part of premedication protocols for anesthesia. Recommended dose rates for butorphanol are 0.02-0.05 mg/kg i.v. in combination with acepromazine (0.05 mg/kg), xylazine (0.5-1.0 mg/kg) or detomidine (10-20 (xg/kg). 

Substitutions of Tic residue in the N-terminal region of DYN were made to ascertain whether it could alter their k-receptor agonist characteristics, converting the resulting peptides into an antagonist. 

Kamei K, Maeda N, Nomura K, Shibata M, Katsuragi-Ogino R, Koyama M, Nakajima M, Inoue T, Ohno T, Tatsuoka T. Synthesis, sar studies, and evaluation of 1,4-benzoxazepine derivatives as selective 5-htla receptor agonists with neuroprotective effect discovery of piclozotan. Bioorg Med Chem 2006 14 1978-1992. 

TAKAHASHI M, MORIGUCHI S, IKENO M, KONO S, OHATA K., USUI H, KURAHASHI K, SASAKI R, YOSHIKAWA M (1996) Studies on the Ueum-contracting mechanisms and identification as a complement C3a receptor agonist of oryzatensin, a bioactive peptide derived from rice albumin. Peptides. 17 5-12. 

Lebel, L. A. Koe, B. K. (1992). Binding studies with the 5-HTlb receptor agonist [3H]CP-96,501 in brain tissues. Drug Devel. Res. 27, 253-64. 

Khroyan T.V., Platt D.M., Rowlett J.K., Spealman R.D. Attenuation of relapse to cocaine seeking by dopamine D1 receptor agonists and antagonists in non-human primates. Psychopharmacology (Berlin). 168 124, 2003. 

Shippenberg T., LeFevour A., Heidbreder C. K-opioid receptor agonists prevent sensitization to the conditioned rewarding effects of cocaine. J. Pharmacol. Exp. Ther. 276 545, 1996. 

Rothman R., France C., Bykov V. et al. Pharmacological activities of optically pure enantiomers of the K opioid agonist, U50,488 and its els diastereomer evidence for three K receptor subtypes. Em J. Pharmacol. 167 345, 1989. 

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