Adinazolam affects biogenic amine release in hippocampal CA1 neuronal circuitry.
The new triazolobenzodiazepine, adinazolam, which has dual anxiolytic and antidepressant activities, was studied for its effects on hippocampal CA1 norepinephrine and serotonin release in chloral hydrate-anesthetized rats, with in vivo voltammetry. Norepinephrine signals were further characterized in vivo by the detection of a significantly increased norepinephrine signal (mean = 25.8%) (p less than 0.003) after intraperitoneal administration of the alpha 2 adrenoreceptor antagonist, yohimbine, and by the detection of a significantly decreased norepinephrine signal (mean = 20.1%) (p less than 0.037) after intraperitoneal administration of the alpha 2 adrenoreceptor agonist, clonidine. Time course studies showed that the anxiolytic-antidepressant drug adinazolam (10 mg/kg IP) significantly decreased hippocampal norepinephrine release (mean = 26.2%) (p less than 0.007). The norepinephrine signal was further significantly decreased by adinazolam (mean = 16.4%) (p less than 0.009) after an additional 2 mg/kg IP injection. Serotonin release, which was detected with norepinephrine in sequence, was also significantly decreased by adinazolam (10 mg/kg IP) (mean = 22.4%) (p less than 0.002). The supplemental dose of adinazolam (2 mg/kg IP), however, did not significantly alter serotonin release any further (p less than 0.307). The findings show that the mechanism of action of adinazolam occurs simultaneously on presynaptic release mechanisms for norepinephrine and for serotonin in CA1 region of hippocampus. These findings implicate that noradrenergic and serotonergic release mechanisms may be responsible in part for the dual anxiolytic-antidepressant efficacy of adinazolam.
Broderick
P A
PA
Department of Pharmacology, City University of New York Medical School, NY.
D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism*; D019946:Propylene Glycol; D011409:Propylene Glycols / Q000494:pharmacology; D011712:Pyramidal Tracts / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D013997:Time Factors; D015016:Yohimbine / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D011409:Propylene Glycols; D001569:Benzodiazepines; D015016:Yohimbine; D012701:Serotonin; D019946:Propylene Glycol; C039668:adinazolam; D003000:Clonidine; D009638:Norepinephrine