Partial agonists inverse

If a compound is an antagonist, it does not mean it also doesn t have efficacy (partial agonists, inverse agonists). 

Allosteric Surmountable Antagonism Orthosteric Partial Agonist Inverse Agonist... 

Ross RA, Gibson TM, Stevenson LA, Saha B, Crocker P, Razdan RK, Pertwee RG (1999b) Structural determinants of the partial agonist-inverse agonist properties of 6 -azidohex-2 -yne-A8-tetrahydrocannabinol at cannabinoid receptors. Br J Pharmacol 128 735-743... 

The same principles (Schild analysis) can be applied to competitive antagonists that demonstrate either positive (partial agonists) or negative (inverse agonists). 

As with Section 6.8.5 (inverse agonists), the pA2 is derived by equating the response produced by the full agonist in the absence of the partial agonist (Equation 6.77 with [B] = 0) to the response in the presence of a concentration of the partial agonist that produces a dose ratio of 2 (by definition, the pA2). For calculation of KB from 10-pA2 ... 

One-way analysis of variance, 229-230, 230f—231f Operational model derivation of, 54-55 description of, 45—47, 46f function for variable slope, 55 for inverse agonists, 221 of agonism, 47f orthosteric antagonism, 222 partial agonists with, 124, 220-221 Opium, 147 Orphan receptors, 180 Orthosteric antagonism... 

Full Inverse agonist 1 Partial Inverse aganist Antagonist 1 Partial agonist Full agonist 1... 

Tables 6.8-6.11 illustrate the wide range of C3 side-chain modified A -THC analogues that have been reported in the literature, together with associated in vitro and in vivo data. The affinity of classical cannabinoid analogues for the CBi receptor has been shown to correlate with depression of spontaneous activity and the production of antinociception, hypothermia and catalepsy in mice, and with psychomimetic activity in humans [93]. However, in some cases, there were unexplained differences between the observed trends in binding affinity and the trends in activity in mouse behavioural models. This may point to differences in efficacy among full agonists, partial agonists and antagonists/inverse agonists, or may reflect differences in in vivo metabolism or blood-brain barrier penetration or a combination of these factors.

Exploring the scheme further, a partial agonist will bind to both R and R but with some preferential affinity for one or the other of the two states. If the preference is for R, the ligand will be a partial inverse agonist, as its presence will reduce the number of receptors in the active state, though not to zero. 

Trent JO, Wang ZX, Murray JL, Shao W, Tamamura H, et al. 2003. Lipid bilayer simulations of CXCR4 with inverse agonists and weak partial agonists. J Biol Chem 278(47) 47136-47144. 

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