The invention relates to synthetic tetrapeptide amide ligands of the kappa opioid receptor and particularly to agonists of the kappa opioid receptor that exhibit low P.sub.450 CYP inhibition and low penetration into the brain. An exemplary synthetic tetrapeptide amide of the invention is D-Phe-D-Phe-D-Leu-(.epsilon.-Me) D-Lys-[4-Amidinohomopiperazine amide]: ##STR00001## Pharmaceutical compositions containing these compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions. Such treatable pain includes visceral pain, neuropathic pain and hyperalgesia. Inflammation associated with conditions such as IBD and IBS, ocular and otic inflammation, other disorders and conditions such as pruritis, edema, hyponatremia, hypokalemia, ileus, tussis and glaucoma are treatable or preventable with the pharmaceutical compositions of the invention.

 
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