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Differentiation of CB1 cannabinoid agonists in rats
Author(s) -
Paronis Carol Anne,
Martin J,
Shaller N,
Thakur G A,
Teng H,
Zvonok A,
Makriyannis A,
Bergman J
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.744.1
Subject(s) - cannabinoid receptor , chemistry , cannabinoid , agonist , pharmacology , cannabinoid receptor agonists , partial agonist , endocrinology , medicine , receptor , biochemistry
Results from GTPγS binding and other in vitro assays suggest that cannabinoid (CB) receptor agonists range in efficacy from partial to full agonists. The present studies compared the in vivo effects of a proposed CB1 full agonist, AM4054, and three potential CB1 partial agonists, BAY 59‐3074, an aminoalkylindole (AAI3), and Δ 9 ‐tetrahydrocannabinol (Δ 9 THC) in female rats. During 6 hr sessions post‐injection AM4054 and BAY 59‐3074 reduced core body temperature by more than 4 0 C and doses required to decrease temperature by 3 o C were 0.13 and 6.7 mg/kg, respectively; neither Δ 9 THC nor AAI3 decreased temperature by more than 2 o C. In a rat tail‐flick assay, AM4054, Δ 9 THC and BAY 59‐3074 all had antinociceptive effects over 6 hr sessions, with respective ED 50 values of 0.13, 6.0, and 7.7 mg/kg; AAI3 produced small, but significant, increases in tail flick latency. Similarly, AM4054, Δ 9 THC and BAY 59‐3074 all had diuretic effects, and the average doses required to yield 15 g/kg urine within 2 hrs were 0.05, 5.3, and 4.9 mg/kg, respectively; AAI3 did not have diuretic effects. All four drugs tested decreased operant responding for sweetened milk at 1‐3 hrs after injection; the respective ED 50 values for AM4054, Δ 9 THC, BAY 59‐3074, and AAI3 were: 0.04, 6.4, 3.8, and 10.2 mg/kg. These data indicate that CB1 agonists may be differentiated according to their profile of behavioral effects in rats. (Supported by PHS Grants DA19205, 15723)