Synthesis of 1,4-disubstituted-2-methylpiperazines and study of their analgesic properties.
A series of N,N-disubstituted-2-methylpiperazines (3a-e) has been synthesized and compounds tested both in vitro and in vivo for their analgesic properties. Binding studies showed that the new compounds are devoid of relevant affinity towards mu receptors. However, compound 3a displayed significant analgesic properties both in the hot plate test and in the mouse phenyl-p-benzoquinone induced abdominal constriction test (MAC), whereas the other derivatives were found active only in MAC test. Moreover, it should be noted that compound 3a elicited a Straub-tail reaction also at the lowest administered dose (10 mg/kg, ip) and this effect was antagonized by naloxone.
Barlocco
D
D
Istituto di Chimica Farmaceutica e Tossicologica, Milano, Italy.
Brunello
N
N
Bernardi
M
M
Cignarella
G
G
D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D004353:Drug Evaluation, Preclinical; D008297:Male; D051379:Mice; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000187:drug effects; D013329:Structure-Activity Relationship
D000700:Analgesics; D010879:Piperazines; D017450:Receptors, Opioid, mu