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 μ 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.