Abstract: In some aspects, the present disclosure provides compounds of the formula: wherein the variables are as defined herein. In some embodiments, these compounds may be used to reduce the pain of a patient. These compounds may be used in pain relief and show an improved pharmaceutical profile relative to other commonly used opiates and opioid derivatives.

Abstract: In some aspects, the present disclosure provides compounds of the formula: wherein the variables are as defined herein. In some embodiments, these compounds may be used to reduce the pain of a patient. These compounds may be used in pain relief and show an improved pharmaceutical profile relative to other commonly used opiates and opioid derivatives.

Abstract: A method for administering an ocular analgesic is described. The method includes the steps of providing a topical analgesic that includes a neo-tryptophan-containing neurotensin analog and applying the topical analgesic to the ocular tissue in a dose of about 0.0001 to about 5 mg, alternatively about 0.0001 to about 3 mg, alternatively about 0.0005 to about 1.2 mg, alternatively about 0.0005 to about 1.0 mg, alternatively about 0.00075 to about 1.0 mg, alternatively about 0.001 mg to about 1.0 mg, alternatively about 0.001 mg to about 0.8 mg, alternatively about 0.001 mg to about 0.7 mg, alternatively about 0.001 mg to about 0.6 mg. Methods of administering a topical analgesic containing a neo-tryptophan-containing neurotensin analog are also described. The topical analgesic can be administered in a patch, gel, lotion, spray, or mist.

Abstract: Ocular analgesics for topical administration are described. The topical ocular analgesic includes a neo-tryptophan-containing neurotensin analog. The topical ocular analgesic may alternatively include a buffered salt solution, a local anesthetic solution, a tissue penetrating agent, and/or an opiate. The neo-tryptophan-containing neurotensin analog may be present in a dose of about 0.0005 to about 1.2 mg.

Abstract: A method for administering an ocular analgesic is described. The method includes the steps of providing a topical analgesic that includes a neo-tryptophan-containing neurotensin analog and applying the topical analgesic to the ocular tissue in a dose of about 0.0001 to about 5 mg, alternatively about 0.0001 to about 3 mg, alternatively about 0.0005 to about 1.2 mg, alternatively about 0.0005 to about 1.0 mg, alternatively about 0.00075 to about 1.0 mg, alternatively about 0.001 mg to about 1.0 mg, alternatively about 0.001 mg to about 0.8 mg, alternatively about 0.001 mg to about 0.7 mg, alternatively about 0.001 mg to about 0.6 mg. Methods of administering a topical analgesic containing a neo-tryptophan-containing neurotensin analog are also described. The topical analgesic can be administered in a patch, gel, lotion, spray, or mist.

Abstract: Ocular analgesics for topical administration are described. The topical ocular analgesic includes a neo-tryptophan-containing neurotensin analog. The topical ocular analgesic may alternatively include a buffered salt solution, a local anesthetic solution, a tissue penetrating agent, and/or an opiate. The neo-tryptophan-containing neurotensin analog may be present in a dose of about 0.0005 to about 1.2 mg.

Abstract: A topical opioid paradigm was developed to determine analgesic peripheral effects of morphine. Topical morphine as well as peptides such as [D-Ala2,MePhe4,Gly(ol)5]enkephalin (DAMGO) produced a potent, dose-dependent analgesia using the radiant heat tailflick assay. The topical drugs potentiated systemic agents, similar to the previously established synergy between peripheral and central sites of action. Local tolerance was rapidly produced by repeated daily topical exposure to morphine. Topical morphine tolerance was effectively blocked by the N-Methyl-D-Aspartate (NMDA) receptors antagonist MK801 and ketamine given either systemically or topically. NMDA receptor antagonists reversed pre-existing morphine tolerance. The activity of topical NMDA antagonists to block local morphine tolerance suggests that peripheral NMDA receptors mediate topical morphine tolerance.

Abstract: The present invention encompasses novel splice variant forms of the mu-opioid receptor-1 (MOR-1) and the polynucleotide sequences encoding the MOR-1 splice variants. The invention further encompasses methods of screening for compositions regulating the MOR-1 splice variant activities and the development of therapeutic modalities directed to regulating activity. Regulation of the MOR-1 splice variant activities may impact the physiologic process of analgesia.

Abstract: A method for administering an ocular analgesic is described. The method includes the steps of providing a topical analgesic that includes a neo-tryptophan-containing neurotensin analog and applying the topical analgesic to the ocular tissue in a dose of about 0.0001 to about 5 mg alternatively about 0.0001 to about 3 mg, alternatively about 0.0005 to about 1.2 mg, alternatively about 0.0005 to about 1.0 mg, alternatively about 0.00075 to about 1.0 mg, alternatively about 0.001 mg to about 1.0 mg, alternatively about 0.001 mg to about 0.8 mg, alternatively about 0.001 mg to about 0.7 mg, alternatively about 0.001 mg to about 0.6 mg. Methods of administering a topical analgesic containing a neo-tryptophan-containing neurotensin analog are also described. The topical analgesic can be administered in a patch, gel, lotion, spray, or mist.

Abstract: The present invention encompasses novel splice variant forms of the mu-opioid receptor-1 (MOR-1) and the polynucleotide sequences encoding the MOR-1 splice variants. The invention further encompasses methods of screening for compositions regulating the MOR-1 splice variant activities and the development of therapeutic modalities directed to regulating activity. Regulation of the MOR-1 splice variant activities may impact the physiologic process of analgesia.

Abstract: The present invention relates to sigma-1 receptor ligands, to uses of sigma-1 receptor ligands in treating drug resistance, methods of using sigma-1 receptor ligands in regulating P-glycoprotein expression, methods of screening for compositions (e.g., agonists) that activate the sigma-1 receptor, regulate P-glycoprotein expression and/or have tolerance reducing activity.

Abstract: The subject invention provides recombinant nucleic acid molecule which encodes a kappa3 opioid receptor, and the receptor encoded thereby. The subject invention further provides related anti-sense oligonucleotide molecules. The subject invention further provides a related host vector system, and method for using same. The subject invention further provides polyclonal and monoclonal antibodies capable of specifically binding to kappa3 opioid receptor, methods for obtaining same, and methods of using same to detect the presence of, and quantitatively determine the amount of, kappa3 opioid receptor in a sample, image and quantitatively determine the amount of cell membrane-bound kappa3 opioid receptor present in a subject, determine a subject's potential sensitivity to a kappa3 opioid receptor-specific agent, determine the affinity of an agent for kappa3 opioid receptor, and identify agonists and antagonists of kappa3 opioid receptor.

Abstract: Compositions useful for long-lasting pain relief from mucosal damage, such as mucosal inflamation, abrasions, ulcerations, lesions, trauma and incisions, without significant systemic absorption. The compositions of the invention are particularly suitable for application to the mucous membrane of the nasal cavity and buccal cavity. To relieve pain, the compositions or the invention are topically applied directly to the affected area.

Abstract: The subject invention provides recombinant nucleic acid molecule which encodes a kappa3 opioid receptor, and the receptor encoded thereby. The subject invention further provides related anti-sense oligonucleotide molecules. The subject invention further provides a related host vector system, and method for using same. The subject invention further provides polyclonal and monoclonal antibodies capable of specifically binding to kappa3 opioid receptor, methods for obtaining same, and methods of using same to detect the presence of, and quantitatively determine the amount of, kappa3 opioid receptor in a sample, image and quantitatively determine the amount of cell membrane-bound kappa3 opioid receptor present in a subject, determine a subject's potential sensitivity to a kappa3 opioid receptor-specific agent, determine the affinity of an agent for kappa3 opioid receptor, and identify agonists and antagonists of kappa3 opioid receptor.

Abstract: The present invention encompasses novel splice variant forms of the mu-opioid receptor-1 (MOR-1) and the polynucleotide sequences encoding the MOR-1 splice variants. The invention further encompasses methods of screening for compositions regulating the MOR-1 splice variant activities and the development of therapeutic modalities directed to regulating activity. Regulation of the MOR-1 splice variant activities may impact the physiologic process of analgesia.

Abstract: Compositions useful for long-lasting pain relief from mucosal damage, such as mucosal inflamation, abrasions, ulcerations, lesions, trauma and incisions, without significant systemic absorption. The compositions of the invention are particularly suitable for application to the mucous membrane of the nasal cavity and buccal cavity. To relieve pain, the compositions or the invention are topically applied directly to the affected area.

Abstract: Compositions useful for long-lasting pain relief from mucosal damage, such as mucosal inflamation, abrasions, ulcerations, lesions, trauma and incisions, without significant systemic absorption. The compositions of the invention are particularly suitable for application to the mucous membrane of the nasal cavity and buccal cavity. To relieve pain, the compositions or the invention are topically applied directly to the affected area.

Abstract: Compositions useful for long-lasting pain relief from mucosal damage, such as mucosal inflamation, abrasions, ulcerations, lesions, trauma and incisions, without significant systemic absorption. The compositions of the invention are particularly suitable for application to the mucous membrane of the nasal cavity and buccal cavity. To relieve pain, the compositions or the invention are topically applied directly to the affected area.

Abstract: The subject invention provides recombinant nucleic acid molecule which encodes a kappa.sub.3 opioid receptor, and the receptor encoded thereby. The subject invention further provides related anti-sense oligonucleotide molecules. The subject invention further provides a related host vector system, and method for using same. The subject invention further provides polyclonal and monoclonal antibodies capable of specifically binding to kappa.sub.3 opioid receptor, methods for obtaining same, and methods of using same to detect the presence of, and quantitatively determine the amount of, kappa.sub.3 opioid receptor in a sample, image and quantitatively determine the amount of cell membrane-bound kappa.sub.3 opioid receptor present in a subject, determine a subject's potential sensitivity to a kappa.sub.3 opioid receptor-specific agent, determine the affinity of an agent for kappa.sub.3 opioid receptor, and identify agonists and antagonists of kappa.sub.3 opioid receptor.

Abstract: Dihydromorphinone compound of the general formulaHDM.dbd.N--Rwherein ##STR1## where * indicates binding carbon R1 is an optionally substituted alkyl, alkylene, cycloalkyl, or cycloalkyleneR2 is OH or HR3 is OH or OCH3 andR is N.dbd.R4, N--R4, ##STR2## R4 is an optionally substituted alkyl, alkylene, cycloalkyl, cycloalkylene, aryl, heterocycloalkyl, heterocycloalkylene, or alkenyl, andn is 1-10, and use thereof as an opiate receptor blocker.