PMID- 24157976
OWN - NLM
STAT- MEDLINE
DCOM- 20140928
LR  - 20240109
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 722
DP  - 2014 Jan 5
TI  - Additive antiemetic efficacy of low-doses of the cannabinoid CB(1/2) receptor 
      agonist Delta(9)-THC with ultralow-doses of the vanilloid TRPV1 receptor agonist 
      resiniferatoxin in the least shrew (Cryptotis parva).
PG  - 147-55
LID - S0014-2999(13)00767-X [pii]
LID - 10.1016/j.ejphar.2013.08.051 [doi]
AB  - Previous studies have shown that cannabinoid CB1/2 and vanilloid TRPV1 agonists 
      (delta-9-tetrahydrocannabinol (Delta(9)-THC) and resiniferatoxin (RTX), respectively) 
      can attenuate the emetic effects of chemotherapeutic agents such as cisplatin. In 
      this study we used the least shrew to demonstrate whether combinations of varying 
      doses of Delta(9)-THC with resiniferatoxin can produce additive antiemetic efficacy 
      against cisplatin-induced vomiting. RTX by itself caused vomiting in a 
      bell-shaped dose-dependent manner with maximal vomiting at 18 mug/kg when 
      administered subcutaneously (s.c.) but not intraperitoneally (i.p.). Delta(9)-THC up 
      to 10 mg/kg provides only 80% protection of least shrews from cisplatin-induced 
      emesis with an ID50 of 0.3-1.8 mg/kg. Combinations of 1 or 5 mug/kg RTX with 
      varying doses of Delta(9)-THC completely suppressed both the frequency and the 
      percentage of shrews vomiting with ID50 dose values 5-50 times lower than 
      Delta(9)-THC doses tested alone against cisplatin. A less potent TRPV1 agonist, 
      capsaicin, by itself did not cause emesis (i.p. or s.c.), but it did 
      significantly reduce vomiting induced by cisplatin given after 30 min but not at 
      2 h. The TRPV1-receptor antagonist, ruthenium red, attenuated cisplatin-induced 
      emesis at 5mg/kg; however, another TRPV1-receptor antagonist, capsazepine, did 
      not. In summary, we present evidence that combination of CB1/2 and TRPV1 agonists 
      have the capacity to completely abolish cisplatin-induced emesis at doses that 
      are ineffective when used individually.
CI  - (c) 2013 Published by Elsevier B.V.
FAU - Darmani, Nissar A
AU  - Darmani NA
AD  - Department of Basic Medical Sciences, College of Osteopathic Medicine of the 
      Pacific, Western University of Health Sciences, 309 East Second Street, Pomona, 
      CA 91766, USA. Electronic address: ndarmani@westernu.edu.
FAU - Chebolu, Seetha
AU  - Chebolu S
AD  - Department of Basic Medical Sciences, College of Osteopathic Medicine of the 
      Pacific, Western University of Health Sciences, 309 East Second Street, Pomona, 
      CA 91766, USA.
FAU - Zhong, Weixia
AU  - Zhong W
AD  - Department of Basic Medical Sciences, College of Osteopathic Medicine of the 
      Pacific, Western University of Health Sciences, 309 East Second Street, Pomona, 
      CA 91766, USA.
FAU - Trinh, Chung
AU  - Trinh C
AD  - Department of Basic Medical Sciences, College of Osteopathic Medicine of the 
      Pacific, Western University of Health Sciences, 309 East Second Street, Pomona, 
      CA 91766, USA.
FAU - McClanahan, Bryan
AU  - McClanahan B
AD  - Department of Basic Medical Sciences, College of Osteopathic Medicine of the 
      Pacific, Western University of Health Sciences, 309 East Second Street, Pomona, 
      CA 91766, USA.
FAU - Brar, Rajivinder S
AU  - Brar RS
AD  - Department of Basic Medical Sciences, College of Osteopathic Medicine of the 
      Pacific, Western University of Health Sciences, 309 East Second Street, Pomona, 
      CA 91766, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131022
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Antiemetics)
RN  - 0 (Cannabinoid Receptor Agonists)
RN  - 0 (Diterpenes)
RN  - 0 (Receptor, Cannabinoid, CB1)
RN  - 0 (Receptor, Cannabinoid, CB2)
RN  - 0 (TRPV Cation Channels)
RN  - 0 (TRPV1 receptor)
RN  - 11103-72-3 (Ruthenium Red)
RN  - 7J8897W37S (Dronabinol)
RN  - A5O6P1UL4I (resiniferatoxin)
RN  - Q20Q21Q62J (Cisplatin)
RN  - S07O44R1ZM (Capsaicin)
SB  - IM
MH  - Animals
MH  - Antiemetics/pharmacology
MH  - Cannabinoid Receptor Agonists/*pharmacology
MH  - Capsaicin/pharmacology
MH  - Cisplatin/adverse effects
MH  - Diterpenes/adverse effects/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Dronabinol/*pharmacology
MH  - Drug Synergism
MH  - Female
MH  - Male
MH  - Receptor, Cannabinoid, CB1/*agonists
MH  - Receptor, Cannabinoid, CB2/*agonists
MH  - Ruthenium Red/pharmacology
MH  - *Shrews
MH  - TRPV Cation Channels/*agonists
MH  - Vomiting/chemically induced/prevention & control
OTO - NOTNLM
OT  - Antiemetic
OT  - Capsaicin
OT  - Capsazepine
OT  - Cisplatin
OT  - Emesis
OT  - Least shrew
OT  - Resiniferatoxin
OT  - Ruthenium red
OT  - Delta(9)-THC
EDAT- 2013/10/26 06:00
MHDA- 2014/10/01 06:00
CRDT- 2013/10/26 06:00
PHST- 2013/04/08 00:00 [received]
PHST- 2013/08/26 00:00 [revised]
PHST- 2013/08/28 00:00 [accepted]
PHST- 2013/10/26 06:00 [entrez]
PHST- 2013/10/26 06:00 [pubmed]
PHST- 2014/10/01 06:00 [medline]
AID - S0014-2999(13)00767-X [pii]
AID - 10.1016/j.ejphar.2013.08.051 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2014 Jan 5;722:147-55. doi: 10.1016/j.ejphar.2013.08.051. Epub 
      2013 Oct 22.