Nonlinear isobologram and superadditive withdrawal from cocaine: cannabinoid combinations in planarians.
Elucidation of interactions between drugs used in polydrug abuse is especially important. However, the necessary experimental conditions for precise quantitative analysis are difficult to establish. Because withdrawal effects of cocaine and the cannabinoid receptor agonist WIN 55212-2 are easily quantified in planarians, demonstration of synergistic effects (P<0.01) of certain ratios of this combination was possible. This synergy, here analyzed with the latest (nonlinear) isobolographic methodology, is now quantitatively established for the first time.
Raffa
Robert B
RB
Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA 19140, USA. robert.raffa@temple.edu
Stagliano
Gregory W
GW
Tallarida
Ronald J
RJ
D000818:Animals; D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D003042:Cocaine / Q000009:adverse effects*; D004357:Drug Synergism; D009025:Morpholines / Q000009:adverse effects*; D009281:Naphthalenes / Q000009:adverse effects*; D010932:Planarians / Q000187:drug effects* / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology
D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D009025:Morpholines; D009281:Naphthalenes; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D003042:Cocaine