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Drugs that stimulate a receptor to a lesser degree are partial agonists or stabilizers. Antagonists are “silent” and only block the action of agonists without having an action of their own. Inverse agonists can block the actions of the agonist, or they can reduce baseline activity in the absence of an agonist. (B) The concept of the agonist spectrum can also be adapted to the signal transduction system. A full agonist leads to maximal signal transduction; a partial agonist leads to a level of signal transduction between the full agonist and no agonist.

These drugs may also increase GABA neurotransmission, enhancing its inhibitory properties. 15. Lamotrigine also acts through a yet unknown mechanism to reduce excitatory glutamate neurotransmission. Similarly to riluzole, lamotrigine may reduce glutamate neurotransmission through actions on voltage-sensitive sodium channels (VSSCs, left) or through as-yet-undefined synaptic actions (right). Modulation of glutamatergic neurotransmission may be related to the efficacy of these compounds to relieve the symptoms of mania.

11. (A) There is currently only one well-established dopamine (DA) partial agonist on the market: aripiprazole. Bifeprunox is a DA partial agonist but was recently not approved by the FDA. Amisulpride and sulpiride are available outside the US and may act as partial agonists, particularly at low doses, but are not well characterized as DA partial agonists. (B) DA partial agonists currently in development include cariprazine/RGH188, bifeprunox, SLV313, SLV314, ACR16, SSR181507, and sarizotan. These agents are closer to the antagonist end of the partial agonist spectrum.

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