Central sites and mechanisms of the hypotensive and bradycardic effects of the narcotic analgesic agent fentanyl.
In dogs, anaesthetized with chloralose, fentanyl (5 mug/kg i.v.) augmented the bradycardia produced by electrical stimulation of the carotid sinus nerves. In contrast, the same dose of the drug did not change the bradycardic response to stimulation of the nucleus of the solitary tract (NTS) indicating that a central facilitation of baroreceptor impulses occurs within the NTS, probably at the first synapse of baroreceptor reflex fibres. Bilateral destruction of the NTS caused a fulminating hypertension and tachycardia similar to that after cutting the baroreceptor afferent fibres. After both procedures, fentanyl (20 mug/kg i.v.) produced marked hypotension and bradycardia. The bradycardic effect was abolished by cutting both vagal nerves when the dogs were pretreated with a beta-adrenoceptor blocking agent (S 2395, 50 mug/kg i.v.). The results provide evidence that the NTS is not the main site of action either for the hypotensive effect or for the vagally mediated bradycardia of fentanyl. Since the dorsal nucleus of the vagal nerve was destroyed together with the NTS, this nucleus does also not appear to be a major site of the action of fentanyl. Blockade of dopamine receptors by haloperidol or pimozide or of serotonin receptors by methysergide did not change the hypotensive, bradycardic and sympathoinhibitory effects of fentanyl.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002346:Carotid Sinus / Q000294:innervation; D003864:Depression, Chemical; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D005283:Fentanyl / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology; D008784:Methysergide / Q000494:pharmacology; D010868:Pimozide / Q000494:pharmacology; D011311:Pressoreceptors / Q000502:physiology*; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D012018:Reflex / Q000187:drug effects; D013153:Splanchnic Nerves / Q000502:physiology; D014630:Vagus Nerve / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D010868:Pimozide; D006220:Haloperidol; D005283:Fentanyl; D008784:Methysergide