Effect of activation of central nervous system serotonin 1A receptors on cardiorespiratory function.
Previous studies indicate that the new antihypertensive drug, urapidil, acts at the ventral surface of the medulla in cats to produce a fall in blood pressure. In addition, urapidil was found in receptor binding studies to have a relatively high affinity for the serotonin 1A receptor. These results suggest that drugs which bind to the serotonin 1A receptor might exert hypotensive effects at the ventral surface of the medulla (VSM). To test this hypothesis, the effects of 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT), the prototype drug for activating serotonin 1A receptors, were evaluated for cardiovascular activity after local application to the VSM. 8-OH-DPAT applied bilaterally to the intermediate area of the VSM in a dose of 1 micrograms/side produced a decrease in mean blood pressure of 60 +/- 7 mm Hg (P less than .05) and a decrease in heart rate of 26 +/- 4 beats/min (P less than .05) (n = 8). Increases in respiratory rate (8 +/- 1 breaths/1 min) and decreases in tidal volume (13 +/- 4 ml) also occurred. These changes were associated with a significant increase in respiratory minute volume (130 +/- 41 ml, P less than .05). Similar cardiorespiratory changes were produced by application of another drug with high affinity for the serotonin 1A receptor, namely B695-40, to the intermediate area of the VSM. Intravenous administration of 8-OH-DPAT in a dose of 100 micrograms/kg mimicked the cardiorespiratory effects of ventral surface application of this agent.(ABSTRACT TRUNCATED AT 250 WORDS)
Gillis
R A
RA
Department of Pharmacology, Georgetown University Medical Center, Washington, District of Columbia.
Hill
K J
KJ
Kirby
J S
JS
Quest
J A
JA
Hamosh
P
P
Norman
W P
WP
Kellar
K J
KJ
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D002415:Cats; D004146:Dioxanes / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects*; D012119:Respiration / Q000187:drug effects*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014498:Uracil / Q000031:analogs & derivatives / Q000494:pharmacology
D004146:Dioxanes; D010879:Piperazines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; C058690:B 695-40; D014498:Uracil; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane