Apparent antinociceptive properties of piperazine-type serotonin agonists: trifluoromethylphenylpiperazine, chlorophenylpiperazine, and MK-212.
Squirrel monkeys were studied under a titration procedure in which responding adjusted the intensity of an electrical stimulus delivered to the tail (0.1-3.3 mA range in 15 steps). The 5-HT agonists trifluoromethylphenylpiperazine (TFMPP), chlorophenylpiperazine (mCPP), and 6-chloro-2(1-piperazinyl)pyrazine (MK-212) increased the intensity at which shock was maintained. The order of potency was: MK-212 greater than mCPP greater than TFMPP. Reductions in absolute rates of responding were small, and not related systematically to increases in shock intensity. Pretreatment with the nonselective 5-HT antagonist methysergide (0.1-1.0 mg/kg) resulted in a 3- to 10-fold shift to the right of the dose-effect curves for the 5-HT agonists. In contrast, the selective 5-HT2 antagonists ketanserin (0.3-1.7 mg/kg) and pirenperone (0.001-0.1 mg/kg) did not alter the effects of these agonists. This suggests that the apparent antinociceptive actions of these 5-HT agonists are probably mediated by effects at the 5-HT1 receptor subtype.
McKearney
J W
JW
Worcester Foundation for Experimental Biology, Shrewsbury, MA 01545.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology*; D011719:Pyrazines / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012453:Saimiri
D010879:Piperazines; D011719:Pyrazines; D011985:Receptors, Serotonin; C018406:1-(3-trifluoromethylphenyl)piperazine; C014896:6-chloro-2-(1-piperazinyl)pyrazine; C015068:1-(3-chlorophenyl)piperazine; D008784:Methysergide