Cardiovascular effects of (-)-11-OH-delta 8-tetrahydrocannabinol-dimethylheptyl in rats.
The effects of the stereochemically pure psychoactive cannabinoid (-)-11-OH-delta 8-tetrahydrocannabinol-dimethylheptyl (HU-210) on blood pressure (BP) and heart rate (HR) were determined in rats. In pentobarbital-anesthetized animals, the compound produced dose-related, long-lasting hypotension and bradycardia at doses between 10 and 1,000 micrograms/kg. BP began to decrease immediately after drug administration, and in no case was an initial pressor response observed. Previous vagotomy (VX) or pretreatment with 6-hydroxydopamine (6-OHDA) did not affect hypotension. Bradycardia was inhibited by VX, but only 60 min after administration of HU-210; it was enhanced by 6-OHDA. The cannabinoid blocked reflex bradycardia induced by phenylephrine (PE). HU-210 also decreased BP and HR in conscious rats. Hypotension lasted 2 h, whereas bradycardia was still present 8 h after drug administration. HU-210 thus shares with delta 9-tetrahydrocannabinol (THC) the ability to decrease BP and HR, but is 5-10 times more potent than the natural compound. Its lack of an initial pressor effect, such as that described for THC, could be related to its specificity for the type-1 cannabinoid (CB1) receptor. Hypotension and bradycardia after HU-210 administration are not due to sympathetic withdrawal. Enhanced parasympathetic tone is involved in bradycardia only at a late stage of the response.
Vidrio
H
H
Department of Pharmacology, School of Medicine, National University of Mexico, D.F., Mexico.
Sánchez-Salvatori
M A
MA
Medina
M
M
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D017704:Baroreflex / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002317:Cardiovascular Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013565:Sympatholytics / Q000494:pharmacology; D014628:Vagotomy
D000889:Anti-Arrhythmia Agents; D002317:Cardiovascular Agents; D018691:Excitatory Amino Acid Antagonists; D013565:Sympatholytics; D013759:Dronabinol; D016627:Oxidopamine; C062018:HU 211