SMLs that might be developed for the treatment of GD are SML TSHR antagonists and SML TSHR inverse agonists
A clinical trial assessing the safety and efficacy of taranabant, a CB1R inverse agonist
, in obese and overweight patients: a high-dose study.
(3) Inverse agonists
bind to the same receptor as a normal neurotransmitter or agonist but induce the opposite effect (rather than just preventing neurotransmitter or agonist actions by blocking their interaction with the receptor).
In any case, Suzdak says, "we hope to develop a more potent analog of the drug--one that would have no inverse agonist
effects at all." For now, his group is planning tests with nonhuman primates to see whether the current drug is useful in blocking the positive reinforcement effects that encourage alcohol dependence in the chronic heavy drinker.
up-regulates the constitutively active D3.49(164)Q mutant of the rat mu-opioid receptor by stabilizing the structure and blocking constitutive internalization and down-regulation.
The patent relates to a class of inverse agonists
to the 5-HT2A serotonin receptor, which is thought to be involved in the regulation of sleep architecture and sleep maintenance.
Based on the finding that clozapine in low dosages acts at 5-HT2A receptors, (7) pimavanserin was designed to be a potent 5-HT2A inverse agonist
, with more than 5-fold higher selectivity over 5-HT2C receptors, and no appreciable affinity for other serotonergic, adrenergic, dopaminergic, muscarinic, or histaminergic receptors (8) (Table 2, page 83).
Arena's lead product candidate for the treatment of insomnia, APD125, a compound with a novel mechanism of action (a selective 5-HT2A receptor inverse agonist
), is scheduled to begin a Phase 2 clinical trial by the end of 2005.
Prior to joining Navitor, Owen served and senior vice president, Clinical Development and Chief Medical officer at Acadia, where he led the development of pimavanserin, a 5HT2a inverse agonist
, for the treatment of Parkinson's disease psychosis, as well as dementia-related psychosis, depression, and schizophrenias.
The pipeline includes CRB-4001, Jenrin's 2nd generation, peripherally-restricted, CB1 inverse agonist
targeting liver, lung, heart and kidney fibrotic diseases.
A study using the selective inverse agonist
pimavanserin (not FDA-approved) decreased akathisia in healthy volunteers taking haloperidol.