1 The present study compares the effects on representative autonomic outflows of IVth ventricular application of
tryptamine analogues which act at
5-HT1 receptors with
8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). 2 Cumulative doses of
8-OH-DPAT, N,N-di-n-propyl-5-carboxamidotryptamine (DP-5-CT) and
5-carboxamidotryptamine (5-CT, 2.5-40 nmol kg-1),
sumatriptan (10-160 nmol kg-1),
indorenate (100-800 nmol kg-1),
5-hydroxytryptamine (5-HT, 20-640 nmol kg-1) both alone and in the presence of
cinanserin (0.1 mg kg-1) were given into the IVth ventricle of cats which were anaesthetized with a mixture of
alpha-chloralose and
pentobarbitone sodium, neuromuscularly blocked and artificially ventilated. Recordings were made of arterial blood pressure, heart rate, renal, cardiac, splanchnic and phrenic nerve activities, femoral arterial flow, tracheal and intragastric pressures. 3 Central application of each of the agonists evoked significant falls in arterial blood pressure. In addition
8-OH-DPAT,
DP-5-CT, 5-CT and
5-HT all evoked a differential inhibition of sympathetic nerve activities, with renal nerve activity being the most sensitive and cardiac nerve activity the least sensitive. In the dose-ranges used, administration of
sumatriptan evoked reductions only in renal and splanchnic nerve activities whilst
indorenate reduced activity in all three sympathetic nerves to a similar extent. 4. The effect of the agonists on heart rate was more inconsistent than the effects on sympathetic outflow.IVth ventricular application of 5-CT and
sumatriptan were without effect on heart rate whilst
8-OH-DPAT,
DP-5-CT,
indorenate and
5-HT alone and in the presence of
cinanserin all evoked significant
bradycardias. However, whilst
atropine partially reversed the
bradycardias evoked by 8-OHDPAT and only slightly reversed those caused by
indorenate,
atropine was without effect on those evoked by
DP-5-CT or 5-HT.5. None of the analogues tested had significant effects on gut motility, phrenic nerve discharge or tracheal pressure.
8-OH-DPAT,
DP-5-CT,
indorenate and
5-HT were without effect on femoral arterial conductance. However, following pretreatment with
cinanserin,
5-HT evoked a significant reduction in femoral arterial conductance. At its highest dose,
sumatriptan evoked a significant increase in femoral arterial conductance as did 5-CT at the 20 nmol kg-1 dose.6. It is concluded that the present data support the view that 5-HT1A receptors at the level of the brainstem are involved in the central sympathoinhibitory effects caused by
intravenous administration of 5-HT1A agonists. Further, brainstem 5-HT1A receptors play an important role in the control of renal sympathetic outflow while brainstem 5-HT2 receptors are involved in the control of skeletal muscle and/or skin blood flow. Selective
tryptamine agonists for 5-HT1A receptors differ from non-
tryptamine agonists in that they do not cause an increase in central cardiac vagal tone.