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Diuretic effects of cannabinoids.
J Pharmacol Exp Ther. 2013 Jan; 344(1):8-14.JP

Abstract

In vivo effects of cannabinoid (CB) agonists are often assessed using four well-established measures: locomotor activity, hypothermia, cataleptic-like effects, and analgesia. The present studies demonstrate that doses of CB agonists that produce these effects also reliably increase diuresis. Diuretic effects of several CB agonists were measured in female rats over 2 hours immediately after drug injection, and results were compared with hypothermic effects. Direct-acting CB1 agonists, including Δ(9)-tetrahydrocannabinol, WIN 55,212 [R-(1)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate], AM2389 [9β-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol], and AM4054 [9β-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol], produced dose-dependent increases in diuresis and decreases in colonic temperature, with slightly lower ED(50) values for diuresis than for hypothermia. The highest doses of cannabinoid drugs yielded, on average, 26-32 g/kg urine; comparable effects were obtained with 10 mg/kg furosemide and 3.0 mg/kg trans-(-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide (U50-488). Methanandamide (10.0 mg/kg) had lesser effect than other CB agonists, and the CB2 agonist AM1241 [1-(methylpiperidin-2-ylmethyl)-3-(2-iodo-5-nitrobenzoyl)indole], the anandamide transport inhibitor AM404, and the CB antagonist rimonabant did not have diuretic effects. In further studies, the diuretic effects of the CB1 agonist AM4054 were similar in male and female rats, displayed a relatively rapid onset to action, and were dose-dependently antagonized by 30 minutes pretreatment with rimonabant, but not by the vanilloid receptor type I antagonist capsazepine, nor were the effects of WIN 55,212 antagonized by the CB2 antagonist AM630 [(6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl) methanone)]. These data indicate that cannabinoids have robust diuretic effects in rats that are mediated via CB1 receptor mechanisms.

Authors+Show Affiliations

Department of Pharmaceutical Sciences, Northeastern University, Mailstop 206, 140TF 360 Huntington Avenue, Boston, MA 02115, USA. c.paronis@neu.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

23019138

Citation

Paronis, Carol A., et al. "Diuretic Effects of Cannabinoids." The Journal of Pharmacology and Experimental Therapeutics, vol. 344, no. 1, 2013, pp. 8-14.
Paronis CA, Thakur GA, Bajaj S, et al. Diuretic effects of cannabinoids. J Pharmacol Exp Ther. 2013;344(1):8-14.
Paronis, C. A., Thakur, G. A., Bajaj, S., Nikas, S. P., Vemuri, V. K., Makriyannis, A., & Bergman, J. (2013). Diuretic effects of cannabinoids. The Journal of Pharmacology and Experimental Therapeutics, 344(1), 8-14. https://doi.org/10.1124/jpet.112.199331
Paronis CA, et al. Diuretic Effects of Cannabinoids. J Pharmacol Exp Ther. 2013;344(1):8-14. PubMed PMID: 23019138.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diuretic effects of cannabinoids. AU - Paronis,Carol A, AU - Thakur,Ganesh A, AU - Bajaj,Shama, AU - Nikas,Spyros P, AU - Vemuri,V Kiran, AU - Makriyannis,Alexandros, AU - Bergman,Jack, Y1 - 2012/09/27/ PY - 2012/9/29/entrez PY - 2012/9/29/pubmed PY - 2013/2/27/medline SP - 8 EP - 14 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 344 IS - 1 N2 - In vivo effects of cannabinoid (CB) agonists are often assessed using four well-established measures: locomotor activity, hypothermia, cataleptic-like effects, and analgesia. The present studies demonstrate that doses of CB agonists that produce these effects also reliably increase diuresis. Diuretic effects of several CB agonists were measured in female rats over 2 hours immediately after drug injection, and results were compared with hypothermic effects. Direct-acting CB1 agonists, including Δ(9)-tetrahydrocannabinol, WIN 55,212 [R-(1)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate], AM2389 [9β-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol], and AM4054 [9β-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol], produced dose-dependent increases in diuresis and decreases in colonic temperature, with slightly lower ED(50) values for diuresis than for hypothermia. The highest doses of cannabinoid drugs yielded, on average, 26-32 g/kg urine; comparable effects were obtained with 10 mg/kg furosemide and 3.0 mg/kg trans-(-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide (U50-488). Methanandamide (10.0 mg/kg) had lesser effect than other CB agonists, and the CB2 agonist AM1241 [1-(methylpiperidin-2-ylmethyl)-3-(2-iodo-5-nitrobenzoyl)indole], the anandamide transport inhibitor AM404, and the CB antagonist rimonabant did not have diuretic effects. In further studies, the diuretic effects of the CB1 agonist AM4054 were similar in male and female rats, displayed a relatively rapid onset to action, and were dose-dependently antagonized by 30 minutes pretreatment with rimonabant, but not by the vanilloid receptor type I antagonist capsazepine, nor were the effects of WIN 55,212 antagonized by the CB2 antagonist AM630 [(6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl) methanone)]. These data indicate that cannabinoids have robust diuretic effects in rats that are mediated via CB1 receptor mechanisms. SN - 1521-0103 UR - https://www.unboundmedicine.com/medline/citation/23019138/Diuretic_effects_of_cannabinoids_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=23019138 DB - PRIME DP - Unbound Medicine ER -