The present invention is directed to non-cytotoxic protein conjugates for inhibition or reduction of exocytic fusion in a nociceptive sensory afferent cell. The protein conjugates comprise: (i) a Targeting Moiety (TM), wherein the TM is an agonist of a receptor present on a nociceptive sensory afferent cell, and wherein the receptor undergoes endocytosis to be incorporated into an endosome within the nociceptive sensory afferent cell; (ii) a non-cytotoxic protease or a fragment thereof, wherein the protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of the nociceptive sensory afferent cell; and (iii) a Translocation Domain, wherein the Translocation Domain translocates the protease or protease fragment from within the endosome, across the endosomal membrane, and into the cytosol of the nociceptive sensory afferent cell wherein the Targeting Moiety is selected from the group consisting of BAM, -endorphin, bradykinin, substance P, dynorphin and/or nociceptin.

The present invention is directed to non-cytotoxic protein conjugates for inhibition or reduction of exocytic fusion in a nociceptive sensory afferent cell. The protein conjugates comprise: (i) a Targeting Moiety (TM), wherein the TM is an agonist of a receptor present on a nociceptive sensory afferent cell, and wherein the receptor undergoes endocytosis to be incorporated into an endosome within the nociceptive sensory afferent cell; (ii) a non-cytotoxic protease or a fragment thereof, wherein the protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of the nociceptive sensory afferent cell; and (iii) a Translocation Domain, wherein the Translocation Domain translocates the protease or protease fragment from within the endosome, across the endosomal membrane, and into the cytosol of the nociceptive sensory afferent cell wherein the Targeting Moiety is selected from the group consisting of BAM, -endorphin, bradykinin, substance P, dynorphin and/or nociceptin.

The present invention is directed to compounds according to formula,

(R.sup.2R.sup.3)-A.sup.1-c(A.sup.2-A.sup.3-A.sup.4-A.sup.5-A.sup.6-A.sup.7-A.sup.8-A.sup.9)-A.sup.10-R.sup.1,

and pharmaceutically-acceptable salts thereof that act as ligands for one or more of the melanocortin receptors, to methods of using such compounds to treat mammals and to pharmaceutical compositions comprising said compounds.

The present invention is directed to compounds according to formula,

(R.sup.2R.sup.3)-A.sup.1-c(A.sup.2-A.sup.3-A.sup.4-A.sup.5-A.sup.6-A.sup.7-A.sup.8-A.sup.9)-A.sup.10-R.sup.1,

and pharmaceutically-acceptable salts thereof that act as ligands for one or more of the melanocortin receptors, to methods of using such compounds to treat mammals and to pharmaceutical compositions comprising said compounds.

Described are Dynorphin A analog compounds and uses thereof for treating pain in humans and lower animals by administering to a human or lower animal in need of treatment. The compounds interact with the bradykinin receptor to relieve pain. Preferred compounds are amphipathic [Des-Arg.sup.7]-dynorphin A peptide analogs and specific cyclic dynorphin A peptide analogs.

Described are Dynorphin A analog compounds and uses thereof for treating pain in humans and lower animals by administering to a human or lower animal in need of treatment. The compounds interact with the bradykinin receptor to relieve pain. Preferred compounds are amphipathic [Des-Arg.sup.7]-dynorphin A peptide analogs and specific cyclic dynorphin A peptide analogs.

Peptides effective as delta opioid receptor agonists and compositions comprising same are provided. Further provided are methods for targeting medical conditions amenable to treatment with an opioid receptor agonist, including but not limited to, conditions involving pain as well as reducing cocaine craving.

Peptides effective as delta opioid receptor agonists and compositions comprising same are provided. Further provided are methods for targeting medical conditions amenable to treatment with an opioid receptor agonist, including but not limited to, conditions involving pain as well as reducing cocaine craving.

The subject invention provides compositions and methods for alleviating pain. Specifically, the subject invention provides pharmaceutical formulations of polymers, and/or their salts, having advantageous ?-opioid receptor binding activity.

The present invention relates to a pharmaceutical composition comprising a cyclotide and a ligand of the kappa opioid receptor (the kOR), or a combination thereof, for use in treating Multiple Sclerosis (MS), in remyelination, in improving CNS lesions, in preventing or reducing demyelination and/or CNS lesions, and/or in treating pain, in particular neuropathic pain and/or pain resulting from/coming along with MS. The present invention further relates to a combination of a cyclotide and a ligand of the kOR and to a pharmaceutical composition comprising said combination. The present invention further relates to a use of a cyclotide for reducing adverse effects of a ligand of the kOR and/or for increasing the potency and/or efficacy of a ligand of the kOR. Further, the present invention relates to a kit comprising a cyclotide and a ligand of the kOR. The present invention further relates to a pharmaceutical composition as part of a kit, wherein a comprised cyclotide and ligand of the kOR are for use in treating MS and related diseases and/or symptoms. The present invention further relates to a kit comprising a pharmaceutical composition comprising a cyclotide and a ligand of the kOR, wherein said pharmaceutical composition and/or said cyclotide and ligand of the kOR is/are for use in treating MS and related diseases and/or symptoms. The invention further relates to (a) novel Viola-type cyclotide(s).