Interaction of morphine with a new alpha2-adrenoceptor agonist in mice.
Finding new chemicals or adjuvants with analgesic effects in the central nervous system is clinically relevant due to the limited number of drugs with these properties. Here, we present PT-31, which is chemically related to 3-benzyl-imidazolidine, with an analgesic profile that results from alpha(2)-adrenoceptor activation. Intraperitoneal administration of PT-31 dose-dependently produced antinociception in the hot plate test, and interacted synergistically with morphine. This effect was completely reversed by yohimbine, a non-selective antagonist of alpha(2)-adrenoceptors, and by BRL 44408, a selective alpha(2A)-adrenoceptor antagonist. The combination of morphine and PT-31 produced greater antinociceptive activity than either alone, and isobolographic analysis revealed a synergistic interaction between these compounds. Docking results confirm the high affinity of the PT-31 ligand at the alpha(2A)-adrenoceptor.


CONCLUSIONS
This study introduces a new analgesic compound (PT-31) that acts via alpha(2A)-adrenoceptor activation. A significant increase in analgesia was observed when co-administered with morphine. PT-31 is an interesting new substance for pain therapy.
Sudo
Roberto T
RT
Programa de Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil. rtsudo@farmaco.ufrj.br
Calasans-Maia
Jorge A
JA
Galdino
Suely L
SL
Lima
Maria C A
MC
Zapata-Sudo
Gisele
G
Hernandes
Marcelo Z
MZ
Pitta
Ivan R
IR
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D054833:Isoindoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D008958:Models, Molecular; D009020:Morphine / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy / Q000378:metabolism; D011897:Random Allocation; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology
C549017:3-(2-chloro-6-fluorobenzyl)-imidazolidine-2,4-dione; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D007093:Imidazoles; D048289:Imidazolidines; D054833:Isoindoles; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; D009020:Morphine; C072125:BRL 44408