scholarly journals Pain, Pathophysiological Mechanisms, and New Therapeutic Options for Alternative Analgesic Agents in Sheep: A Review and Investigation

Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 909
Author(s):  
Bogdan Feliks Kania ◽  
Danuta Wrońska ◽  
Urszula Bracha
Keyword(s):  
Visceral Pain ◽  
Receptor Antagonists ◽  
Narcotic Analgesics ◽  
Colonic Wall ◽  
Veterinary Ethics ◽  
Cholecystokinin Receptor ◽  
Guiding Principle ◽  
Relieve Pain ◽  
Analgesic Agents ◽  
Narcotic Drugs

Relief from suffering is the guiding principle of medical and veterinary ethics. Medical care for animals should be carried out to meet all welfare conditions. The need for pain management is demonstrated by recent monographs devoting attention to this urgent ethical need. Little data, however, are available on the prevention and attenuation of pain in sheep. After administration of narcotic analgesics used for severe visceral pain, sheep react with a state of excitement. Therefore, it was decided to experimentally investigate the usefulness of potential non-narcotic drugs to relieve pain in sheep with intestinal colic caused by 10 min of mechanical distension of their duodenal and/or descending colonic wall. The results indicate the potential usefulness of VGCCIs (diltiazem, nifedipine, verapamil), cholecystokinin receptor antagonists (PD, proglumide), and metabotropic glutaminergic receptor antagonists (mGluRAs), such as L-AP3, DL-AP3. As a premedication, these substances prevented the occurrence of symptoms of acute intestinal pain including atony of reticulo-rumen, tachycardia, hyperventilation, moaning, gnashing of teeth, hypercortisolemia, and catecholaminemia; hence, these substances are considered potential agents in the treatment of sheep visceral pain.

scholarly journals A selective adenylyl cyclase 1 inhibitor relieves pain without causing tolerance

2021 ◽  
Author(s):  
Gianna Giacoletti ◽  
Tatum Price ◽  
Lucas V. B. Hoelz ◽  
Abdulwhab Shremo Msdi ◽  
Katerina Vazquez-Falto ◽  
...  
Keyword(s):  
Visceral Pain ◽  
Therapeutic Potential ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Selective Inhibitor ◽  
Adenylyl Cyclases ◽  
Analgesic Tolerance ◽  
Relieve Pain ◽  
Analgesic Agents ◽  
Knockout Animals

Adenylyl cyclases (ACs) catalyze the production of the second messenger cyclic adenosine monophosphate from adenosine triphosphate. Among the ten different AC isoforms, studies with knockout animals indicate that inhibition of AC1 can relieve pain and reduce behaviors linked to opioid dependence. We previously identified ST034307 as a selective inhibitor of AC1. The development of an AC1-selective inhibitor now provides the opportunity to further study the therapeutic potential of inhibiting this protein in pre-clinical animal models of pain and related adverse reactions. In the present study we have shown that ST034307 relieves pain in mouse models of formalin-induced inflammatory pain, acid-induced visceral pain, and acid-depressed nesting. In addition, ST034307 did not cause analgesic tolerance after chronic dosing. We also show that the compound is restricted to the periphery following subcutaneous injections and report the predicted molecular interaction between ST034307 and AC1. Our results indicate that AC1 inhibitors represent a promising new class of analgesic agents that treat pain and appear to produce less adverse effects than currently-used opioids.

Inhibition of gastrin-stimulated growth of gastrointestinal tumour cells by octreotide and the gastrin/cholecystokinin receptor antagonists, proglumide and lorglumide

1992 ◽  
Vol 28 (8-9) ◽  
pp. 1462-1467 ◽  
Author(s):  
Susan A. Watson ◽  
David L. Morris ◽  
Lindy G. Durrant ◽  
John F. Robertson ◽  
Jack D. Hardcastle
Keyword(s):  
Tumour Cells ◽  
Receptor Antagonists ◽  
Cholecystokinin Receptor

Synthesis of pseudopeptide cholecystokinin receptor antagonists

Peptides 1994 ◽  
1995 ◽  
pp. 656-657
Author(s):  
J. C. Califano ◽  
M. Amblard ◽  
J. A. Fehrentz ◽  
M. F. Lignon ◽  
N. Bernad ◽  
...  
Keyword(s):  
Receptor Antagonists ◽  
Cholecystokinin Receptor

Cholecystokinin Receptor Antagonists: Ability to Distinguish Various Classes of Cholecystokinin Receptors

1990 ◽  
pp. 95-113 ◽  
Author(s):  
Robert T. Jensen ◽  
Shih Che Huang ◽  
Tammo von Schrenck ◽  
Stephen A. Wank ◽  
Jerry D. Gardner
Keyword(s):  
Receptor Antagonists ◽  
Cholecystokinin Receptor ◽  
Cholecystokinin Receptors

New proglumide-analogue CCK receptor antagonists: very potent and selective for peripheral tissues

1986 ◽  
Vol 250 (6) ◽  
pp. G856-G860 ◽  
Author(s):  
C. Niederau ◽  
M. Niederau ◽  
J. A. Williams ◽  
J. H. Grendell
Keyword(s):  
Agonist Activity ◽  
Receptor Antagonists ◽  
Maximal Inhibition ◽  
Amylase Release ◽  
Peripheral Tissues ◽  
Pancreatic Acini ◽  
Cholecystokinin Receptor ◽  
Low Concentrations ◽  
Competitive Kinetics ◽  
Cck Receptor Antagonists

The present study evaluates the ability of two recently synthesized analogues of proglumide, both 4-benzamido-N,N-di-alkyl-glutaramic acid derivatives, to act as cholecystokinin receptor antagonists. Both new antagonists inhibited cholecystokinin-stimulated amylase release and, similarly, binding of 125I-cholecystokinin to isolated rat pancreatic acini. These effects displayed competitive kinetics; both antagonists showed no agonist activity and were specific in that only those secretagogues were inhibited that interact with the cholecystokinin receptor. Both antagonists also inhibited binding of 125I-cholecystokinin to mouse pancreatic membrane particles similarly to results with rat pancreatic acini. With the more potent of the two new antagonists, half-maximal inhibition of action and binding of cholecystokinin was observed with low concentrations of approximately 10(-7) M; compared with proglumide, the new antagonists were as much as 4,000 times more potent. Unlike proglumide, which inhibits binding of cholecystokinin to pancreas and brain tissue similarly, both antagonists inhibited binding of cholecystokinin to the pancreas at much lower concentrations compared with brain. The more potent of the inhibitors was 300 times more potent in inhibiting binding of cholecystokinin to pancreatic tissues compared with brain.

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