title: Synthesis and pharmacological effects in mice of halogenated cannabinol derivatives.
abstract: Eight halogenated derivatives of cannabinol (CBN) substituted on the aromatic ring at the 2 and/or 4 position were synthesized and their pharmacological effects were evaluated by intracerebroventricular injection (50 micrograms/mouse) in mice, using hypothermia, pentobarbital-induced sleep prolongation, catalepsy and anticonvulsant effect as indices. The hypothermic effects of monohalogenated derivatives of CBN were comparable to that of CBN, whereas the effects of dihalogenated derivatives of CBN except for the fluorinated derivative were attenuated. In the interaction with pentobarbital, two monochlorinated derivatives exhibited a significant prolongation of sleeping time, although other derivatives did not significantly affect the sleeping time. The cataleptogenic effects of monofluoro- and 4-bromo-CBN were stronger than that of CBN. 4-Bromo-CBN exhibited a significant prolongation of seizure latency induced by pentylenetetrazol. These data suggest that halogenation of CBN modifies the pharmacological profile of the cannabinoid.
authors.affiliation: Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yoshida
authors.forename: N
authors.initials: N
authors.lastname: Usami
authors.forename: Y
authors.initials: Y
authors.lastname: Ohishi
authors.forename: K
authors.initials: K
authors.lastname: Watanabe
authors.forename: I
authors.initials: I
authors.lastname: Yamamoto
authors.forename: H
authors.initials: H
authors.lastname: Yoshimura
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000494:pharmacology; D002187:Cannabinol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002375:Catalepsy / Q000139:chemically induced; D006219:Halogens / Q000737:chemistry*; D007035:Hypothermia / Q000139:chemically induced; D007276:Injections, Intraventricular; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D012890:Sleep / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000927:Anticonvulsants; D006219:Halogens; D002187:Cannabinol