Abstract |
New substances designed for the treatment of anxiety have previously been synthesized, which resulted in the identification of four new pyrazolo[3,4-b]pyrrolo[3,4-d] pyridine derivatives structurally designed by using zolpidem as lead compound. Among them, LASSBio-873 was the most potent to produce analgesic, sedative and hypnotic effects. Thus, we investigated the possible mechanisms involved in LASSBio-873-induced sedation, as well as its effects on different models of inflammatory pain. LASSBio-873 (4 mg/kg) reduced locomotor activity of mice in the open field test from 205.2+/-25.6 to 87.6+/-16.2 movements/min. Atropine, a non-selective muscarinic antagonist, prevented the LASSBio-873-induced sedation and increased locomotor activity to 192.9+/-30.2 movements/min. In the formalin test, LASSBio-873 (4 mg/kg) significantly reduced the duration of nociceptive behavior during the inflammatory phase, reducing the control reactivity from 197.6+/-14.5s to 84.4+/-10.3s. Carrageenan reduced the latency for the animal reaction from 5.1+/-0.2s (control) to 2.1+/-0.3s which was completely reverted by LASSBio-873 (6 mg/kg) to 5.6+/-0.6s. Atropine prevented the LASSBio-873-induced antinociceptive and antihyperalgesic activities, indicating the interference of the cholinergic system. LASSBio-873 is a novel prototype of drug that modulates muscarinic activity and could be used for neuropsychiatric and cognitive disorders and other conditions associated to acute and chronic pain.
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Authors | Thaiana C F Mendes, Juliana M Raimundo, Nailton M Nascimento-Junior, Carlos A M Fraga, Eliezer J Barreiro, Roberto T Sudo, Gisele Zapata-Sudo |
Journal | Pharmacology, biochemistry, and behavior
(Pharmacol Biochem Behav)
Vol. 94
Issue 1
Pg. 70-4
(Nov 2009)
ISSN: 1873-5177 [Electronic] United States |
PMID | 19635495
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Adrenergic alpha-Antagonists
- Analgesics
- GABA Antagonists
- Hypnotics and Sedatives
- LASSBio-873
- Muscarinic Antagonists
- Narcotic Antagonists
- Pyrazoles
- Pyridines
- Pyrroles
- Receptors, Muscarinic
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Topics |
- Adrenergic alpha-Antagonists
(metabolism)
- Analgesics
(administration & dosage, pharmacology)
- Analysis of Variance
- Animals
- Behavior, Animal
(drug effects)
- Dose-Response Relationship, Drug
- Exploratory Behavior
(drug effects)
- GABA Antagonists
(metabolism)
- Hot Temperature
- Hyperalgesia
(drug therapy)
- Hypnotics and Sedatives
(administration & dosage, pharmacology)
- Inflammation
(chemically induced, physiopathology)
- Male
- Mice
- Motor Activity
(drug effects)
- Muscarinic Antagonists
(metabolism)
- Narcotic Antagonists
(metabolism)
- Pain
(drug therapy)
- Pain Measurement
- Pyrazoles
(administration & dosage, pharmacology)
- Pyridines
(administration & dosage, pharmacology)
- Pyrroles
(administration & dosage, pharmacology)
- Receptors, Muscarinic
(metabolism)
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