Alpha-adrenergic blockade: a possible mechanism of tocolytic action of certain benzodiazepines in a postpartum rat model in vivo.
Benzodiazepines are frequently used for the treatment of maternal psychiatric disorders during pregnancy. Besides their anxiolytic effect, they are reported to exert a direct relaxing action on several smooth muscle preparations, including the uterus. In the present study, the possibility of the involvement of alpha(1)-adrenergic receptors in this peripheral effect is investigated. The tocolytic potencies of diazepam, midazolam and nitrazepam are assessed in vivo in a postpartum rat model, together with other drugs known to bind to alpha-adrenoceptors (e.g. alpha(1)-antagonists, tricyclic compounds and droperidol). The interactions of some benzodiazepines and norepinephrine were also examined in an isolated in vitro system. The affinities of these agents for the receptor in question were additionally tested by radioligand displacement assay. A correlation was found between the tocolytic potencies and inhibition constants of the tested drugs, suggesting that the smooth muscle-relaxing effect of these benzodiazepines is mediated through modulation of the alpha(1)-adrenergic receptors.
Zupkó
István
I
Department of Pharmacodynamics and Biopharmacy, University of Szeged, Albert Szent-Györgyi Medical and Pharmaceutical Center, H-6720, Eötvös u. 6., Szeged, Hungary.
Jánossy
Kinga
K
Maul
Katalin
K
Márki
Arpád
A
Falkay
George
G
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism; D009567:Nitrazepam / Q000494:pharmacology; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D049590:Postpartum Period; D011247:Pregnancy; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects; D015149:Tocolytic Agents / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1; D015149:Tocolytic Agents; D001569:Benzodiazepines; D009567:Nitrazepam; D003975:Diazepam; D009638:Norepinephrine