Evidence suggesting that the 5-HT2 antagonist ICI 169,369 activates vagal afferents and in addition has a central hypotensive action in anaesthetized rats.
1. The cardiovascular effects of the 5-HT2 antagonist ICI 169,369 have been investigated in pentobarbitone anaesthetized rats and in pithed rats whose blood pressure was supported by a vasopressin infusion. 2. In anaesthetized rats, cumulative doses (0.1-3.0 mg kg-1) of ICI 169,369 caused dose-related large transient falls in heart rate and blood pressure followed by a slow dose-related decline in both parameters. 3. Pretreatment with atropine methonitrate (1 mg kg-1) alone or in combination with atenolol (1 mg kg-1) or bi-vagotomy blocked the transient changes in blood pressure and heart rate caused by ICI 169,369. The long-term fall in heart rate was also attenuated by either atropine or atenolol; however, the combination of atenolol and atropine was more effective. None of the above pretreatments affected the long-term fall in blood pressure caused by ICI 169,369. 4. The cardiovascular effects of ICI 169,369 were unaffected by pretreatment with MDL 72222 (1 mg kg-1) and failed to show cross-tachyphylaxis with phenylbiguanide. 5. In pithed rats whose blood pressure was maintained with vasopressin, ICI 169,369 failed to cause any of the above transient and long-term effects on blood pressure and heart rate. 6. The study indicates that ICI 169,369 is capable of stimulating cardiopulmonary afferents through a non 5-HT3 receptor mechanism and has a central hypotensive action.
Pires
J G
JG
Academic Department of Pharmacology, Royal Free Hospital School of Medicine, Hampstead, London, UK.
Ramage
A G
AG
D000344:Afferent Pathways / Q000187:drug effects; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects; D003655:Decerebrate State / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014630:Vagus Nerve / Q000187:drug effects*
D011804:Quinolines; D012702:Serotonin Antagonists; C054363:2-((2-(dimethylamino)ethyl)thio)-3-phenylquinoline