| Stereochemistry | ACHIRAL |
| Molecular Formula | C9H9Cl2N3 |
| Molecular Weight | 230.094 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
ClC1=CC=CC(Cl)=C1NC2=NCCN2
InChI
InChIKey=GJSURZIOUXUGAL-UHFFFAOYSA-N
InChI=1S/C9H9Cl2N3/c10-6-2-1-3-7(11)8(6)14-9-12-4-5-13-9/h1-3H,4-5H2,(H2,12,13,14)
| Molecular Formula | C9H9Cl2N3 |
| Molecular Weight | 230.094 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
Clonidine is a centrally acting α2 adrenergic agonist and imidazoline receptor agonist used to treat high blood pressure, attention deficit hyperactivity disorder, anxiety disorders, tic disorders, withdrawal (from either alcohol, opioids, or smoking), migraine, menopausal flushing, diarrhea, and certain pain conditions. Clonidine treats high blood pressure by stimulating α2 receptors in the brain, which decreases peripheral vascular resistance, lowering blood pressure. It has specificity towards the presynaptic α2 receptors in the vasomotor center in the brainstem. This binding decreases presynaptic calcium levels, thus inhibiting the release of norepinephrine (NE). It has also been proposed that the antihypertensive effect of clonidine is due to agonism on the I1 receptor (imidazoline receptor), which mediates the sympatho-inhibitory actions of imidazolines to lower blood pressure. Clonidines mechanism of action in the treatment of ADHD is to increase noradrenergic tone in the prefrontal cortex (PFC) directly by binding to postsynaptic α2A adrenergic receptors and indirectly by increasing norepinephrine input from the locus coeruleus. Clonidine indicated in the treatment of hypertension. Clonidine hydrochloride tablets may be employed alone or concomitantly with other antihypertensive agents. The US Food and Drug Administration (FDA) has approved clonidine for the treatment of attention deficit hyperactivity disorder (ADHD), under the trade name of Kapvay alone or with stimulants in 2010, for pediatric patients aged 6–17 years.
CNS Activity
Originator
Approval Year
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
Drug as victim
Tox targets
Sourcing
Sample Use Guides
Oral
Initial Dose 0.1 mg tablet twice daily (morning and bedtime). Elderly patients may benefit from a lower initial dose
Maintenance Dose Further increments of 0.1 mg per day may be made at weekly intervals if necessary until the desired response is achieved. Taking the larger portion of the oral daily dose at bedtime may minimize transient adjustment effects of dry mouth and drowsiness. The therapeutic doses most commonly employed have ranged from 0.2 mg to 0.6 mg per day given in divided doses. Studies have indicated that 2.4 mg is the maximum effective daily dose, but doses as high as this have rarely been employed.
Transdermal: once every 7 days to a hairless area of intact skin on the upper outer arm or chest.
Route of Administration:
Other
Neural membranes (P2 fractions) were prepared from the prefrontal cortex of human brains obtained at autopsy. Specific Clonidine binding was measured in 0.55 mL aliquots (50 mM Tris HCl, pH 7.5) of the neural membranes, which were incubated with [3H]RX821002 (1 nM) for 30 min at 25 °C in the absence or presence of the Clonidine (10^-12 M to 10^-3 M, 10 concentrations). Specific binding was determined and plotted as a function of the compound concentration. Incubations were terminated by diluting the samples with 5 mL of ice-cold Tris incubation buffer (4 °C). Membrane-bound [3H]RX821002 was separated by vacuum filtration through Whatman GF/C glass fiber filters. Then the filters were rinsed twice with 5 mL of incubation buffer and transferred to minivials containing 3 mL of OptiPhase “HiSafe” II cocktail and counted for radioactivity by liquid scintillation spectrometry.
