Centrally-mediated cardiovascular effects of 5-hydroxytryptophan in MAO-inhibited dogs: modification by autonomic antagonists.
In MAO-inhibited dogs, 5-hydroxytryptophan (5-HTP), either 5 or 10 mg/kg i.v., caused hypotension with variable effects on heart rate. Reflex responses to bilateral carotid artery occlusion (BCO) were greatly inhibited by 5-HTP. The hypotensive effects were markedly inhibited by cerebral and extracerebral decarboxylase inhibition with RO 4-4602 and the inhibition of BCO was delayed. Selective extracerebral decarboxylase inhibitation with MK 486 did not prevent either the hypotensive action of 5-HTP or the effect on BCO, although the amino acid now consistently caused bradycardia. Left ventricular pressure and dP/dt were reduced, but cardiac output was maintained by an increase in stroke volume. Hypotension was due predominantly to decreased peripheral resistance. The hypotensive action of 5-HTP was abolished or greatly attenuated after pretreatment with either yohimbine or methysergide, but was unaffected by haloperidol. These results indicate that cerebral decarboxylation and formation of 5-HT are responsible for the hypotension after 5-HTP in MAO inhibited dogs.
D006916:5-Hydroxytryptophan / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001337:Autonomic Agents / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D013997:Time Factors; D015016:Yohimbine / Q000494:pharmacology
D001337:Autonomic Agents; D008996:Monoamine Oxidase Inhibitors; D015016:Yohimbine; D006916:5-Hydroxytryptophan; D006220:Haloperidol; D008784:Methysergide