Lofexidine is a centrally acting alpha2-adrenergic agonist used for the symptomatic treatment of acute opioid withdrawal syndrome to facilitate abrupt opioid discontinuation in adults. It was first studied for use as an antihypertensive in 1980, but its researched was stopped as it was found less effective for the treatment of hypertension than clonidine.
- Mechanism
- Curator reviewed · 4 references
Lofexidine is a potent alpha2-adrenergic receptor agonist with some moderate agonistic affinity towards Alpha-1A adrenergic receptor and 5-HT1a, 5-HT7, 5HT2c and 5HT1d receptors.
The alpha2-adrenergic receptor is normally targeted by norepinephrine and its activation inhibits the synthesis of cAMP which in turn leads to potassium efflux and suppression of neural firing and inhibition of norepinephrine release. All of this activity can reduce the heart rate, blood pressure, and attenuate sympathetic stress response.
Opioids inhibit cAMP in the noradrenergic neurons and their discontinuation produces a rise in the level of cAMP. This will generate an increase in norepinephrine which is associated with the symptoms of withdrawal. The magnitude of the effect is augmented by chronic opioid use due to the compensatory mechanisms of continuous negative feedback. Therefore, chronic opioid use translates into an exacerbated production of cAMP and norepinephrine release.
Lofexidine replaces the opioid-driven inhibition of cAMP production by activating the alpha2-adrenergic receptor and moderating the symptoms of opioid withdrawal. This effect is performed without interacting with opioid receptors which mediate other activities of opioid dependence or addiction.
- Primary indication
- Lofexidine is indicated for mitigation of symptoms associated with acute withdrawal from opioids and for facilitation of the completion of opioid discontinuation treatment.Curator reviewed · 1 structured indication
- Formula / weight
- C11H12Cl2N2O · 259.132 g/mol (avg)
- First approval
- United States, 2018
- Brand names
Resolves to
KSMAGQUYOIHWFS-UHFFFAOYSA-NSMILESCC(OC1=C(Cl)C=CC=C1Cl)C1=NCCN1What you can answer from here — as of August 30, 2026
Which drugs share a target with Lofexidine, and which of those have an active Phase 3 trial?
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