Linked Life Data

7776826

Source:http://linkedlifedata.com/resource/pubmed/id/7776826

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23-24
pubmed:dateCreated
1995-7-11
pubmed:abstractText
A series of 3-alkyl-2'-yne (side chain) acetylenic analogs of delta 9-THC were synthesized and evaluated for in vitro and in vivo activity. Analogs were evaluated for receptor affinity in a [3H]CP-55,940 displacement assay and for in vivo pharmacological activity in a mouse procedure utilizing a tetrad of measures. These compounds represent a preliminary exploration of the consequences of restricting the flexibility of the side chain regarding cannabimimetic activity. All analogs proved to have receptor affinities (4-11 nM) that were five to ten times greater than that observed for delta 9-THC. However, the in vivo activities of these compounds varied greatly. All analogs proved to possess the greatest potency for production of antinociception, with activity similar to or less than that observed for the production of hypomotility, hypothermia, and catalepsy. The most potent analog 11b exhibited an ED50 of 0.031 mg/kg in the tail-flick procedure, with values in other measures being between 0.5 and 1.0 mg/kg. The least active compound (11c), though still possessing a KI of 11 nM, exhibited ED50 values of 3.1 and 9.3 mg/kg for tail-flick and temperature procedures, as well as 41 and 48 mg/kg for ring-immobility and spontaneous locomotor activity, respectively. This profile (high receptor affinity but low in vivo potency) would normally be suggestive of a compound with antagonist properties (at least for immobility and activity measures). It is unclear why these acetylenic analogs were so potent in vitro, while only one (11b) exhibited the degree of in vivo potency anticipated based upon comparison to values for delta 9-THC. It is possible these side chain modifications do not interfere with receptor recognition, but limit receptor activation or second messenger signal transduction. Regardless, it is clear these novel analogs provide a basis for the further exploration of the cannabinoid receptor pharmacophore.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0024-3205
pubmed:author
pubmed:issnType
Print
pubmed:volume
56
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2013-20
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
A novel class of potent tetrahydrocannabinols (THCS): 2'-yne-delta 8- and delta 9-THCS.
pubmed:affiliation
Organix, Inc., Woburn, MA 01801, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.