Faculty Opinions recommendation of Dynorphin--still an extraordinarily potent opioid peptide.

Author(s):  
Rita Valentino
Keyword(s):  
Author(s):  
George D. Pappas ◽  
Jacqueline Sagen

We have been interested in the use of neural transplants mainly as a local source of neuroactive substances, rather than as a replacement for damaged neural circuities. In particular, we have been exploring the possibilities of reducing pain by transplants of opioid peptide producing cells, and reducing depression by transplants of monoamine-producing cells. For the past several years, work in our laboratory has demonstrated in both acute and chronic pain models that transplantation of adrenal medullary tissue or isolated chromaffin cells into CNS pain modulatory regions can reduce pain sensitivity in rodents. Chromaffin cells were chosen as donor source since they produce high levels of both opioid peptides and catecholamines, substances which independently, and probably synergistically, reduce pain sensitivity when injected locally into the spinal cord. The analgesia produced by these transplants most likely results from the release of both opioid peptides and catecholamines, since it can be blocked or attenuated by opiate or adrenergic antagonists, respectively. Furthermore, CSF levels of met-enkephalin and catecholamines are increased by the transplants.


Analgesia ◽  
1995 ◽  
Vol 1 (4) ◽  
pp. 390-393 ◽  
Author(s):  
Dominic M. Desiderio ◽  
Lin Yan ◽  
Genevieve Fridland ◽  
Jih-Lie Tseng

Analgesia ◽  
1999 ◽  
Vol 4 (1) ◽  
pp. 27-32 ◽  
Author(s):  
John S. Partilla ◽  
F. Ivy Carrol ◽  
James B. Thomas ◽  
Kenner C. Rice ◽  
Dennis M. Zimmerman ◽  
...  

2010 ◽  
Vol 13 (2) ◽  
pp. 20-31
Author(s):  
Ayad A. AL-Hamashi ◽  
◽  
Kawkab Y. Saour ◽  

Circulation ◽  
1997 ◽  
Vol 95 (8) ◽  
pp. 2122-2129 ◽  
Author(s):  
Salvatore Pepe ◽  
Rui-Ping Xiao ◽  
Charlene Hohl ◽  
Ruth Altschuld ◽  
Edward G. Lakatta

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 927
Author(s):  
KK DurgaRao Viswanadham ◽  
Roland Böttger ◽  
Lukas Hohenwarter ◽  
Anne Nguyen ◽  
Elham Rouhollahi ◽  
...  

Opioids account for 69,000 overdose deaths per annum worldwide and cause serious side effects. Safer analgesics are urgently needed. The endogenous opioid peptide Leu-Enkephalin (Leu-ENK) is ineffective when introduced peripherally due to poor stability and limited membrane permeability. We developed a focused library of Leu-ENK analogs containing small hydrophobic modifications. N-pivaloyl analog KK-103 showed the highest binding affinity to the delta opioid receptor (68% relative to Leu-ENK) and an extended plasma half-life of 37 h. In the murine hot-plate model, subcutaneous KK-103 showed 10-fold improved anticonception (142%MPE·h) compared to Leu-ENK (14%MPE·h). In the formalin model, KK-103 reduced the licking and biting time to ~50% relative to the vehicle group. KK-103 was shown to act through the opioid receptors in the central nervous system. In contrast to morphine, KK-103 was longer-lasting and did not induce breathing depression, physical dependence, and tolerance, showing potential as a safe and effective analgesic.


2017 ◽  
Vol 32 (1) ◽  
pp. 444-451 ◽  
Author(s):  
Adriano Mollica ◽  
Sveva Pelliccia ◽  
Valeria Famiglini ◽  
Azzurra Stefanucci ◽  
Giorgia Macedonio ◽  
...  

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