Involvement of the opioid receptors in the sedative, antinociceptive and potentiating effects with benzodiazepines of the glycosilated flavonoid hesperidin

LEONARDO M. LOSCALZO; CRISTINA WASOWSKI; ALEJANDRO C. PALADINI; MARIEL MARDER

Buenos Aires, Argentina.

Congreso; XXXIX Reunión annual de la Sociedad Argentina de Farmacología Experimental; 2007

Previous studies performed in our laboratories reported the sedative and the sleep enhancing activities of hesperidin (hesperetin-7-rhamnoglucoside). These properties are greatly increased when the glycoside is injected jointly with diazepam and this interaction has been shown to be synergistic. In this work we demonstrate that this effect is shared with various benzodiazepines, among them alprazolam, bromazepam, midazolam and flunitrazepam, which were used to study the potentiation with hesperidin as measured in the hole board and the locomotor activity tests. We have also proved that the behavioral and synergistic effects induced by hesperidin do not involve classical GABAA receptors. In addition, it has been demonstrated that hesperidin possesses anti-inflammatory and analgesic activities. In order to get going in the study of the mechanism of action of hesperidin, we explore the possible participation of other brain receptors, namely opioid, serotonin and alpha 1-adrenergic. The use of opioid antagonists in the present work provided the first experimental evidence of the participation of those receptors in the sedative, antinociceptive and potentianting effects of hesperidin with benzodiazepines in mice.