Guanfacine

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Structural formula
Structural formula of guanfacine
General
Surname Guanfacine
other names

N - (diaminomethylidene) -2- (2,6-dichlorophenyl) acetamide

Molecular formula C 9 H 9 Cl 2 N 3 O
External identifiers / databases
CAS number
  • 29110-47-2 (guanfacine)
  • 29110-48-3 (guanfacine hydrochloride )
PubChem 3519
DrugBank DB01018
Wikidata Q5613599
Drug information
ATC code

C02 AC02

properties
Molar mass 246.09 g · mol -1
Physical state

firmly

Melting point

211-215 ° C

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
06 - Toxic or very toxic

danger

H and P phrases H: 301
P: 264-270-301 + 310 + 330-405-501
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Guanfacine is a drug from the group of antisympathotonics . In low doses, it sustained lower blood pressure. In addition to the treatment of high blood pressure , guanfacine is also used in the treatment of attention deficit / hyperactivity disorder (ADHD). It is effective orally .

In ADHD, it shows a larger effect size than atomoxetine , but a smaller one than stimulants .

application areas

Guanfacine is a derivative of clonidine and was originally used to treat high blood pressure. It reduced blood pressure by around 16%, but was unable to maintain its position on the market as a blood pressure lowering agent after more modern antihypertensive drugs with a more favorable risk-benefit ratio had been developed.

Since September 2015, guanfacine has been approved in the European Union for the treatment of ADHD in 6 to 17 year olds for whom treatment with stimulants is not an option , is not tolerated or was ineffective. Guanfacine is usually administered in a delayed form and may only be used as part of an overall therapeutic strategy, which usually also includes psychological, educational and social measures.

Studies have also shown guanfacine to be effective in 2 and 3 year old children.

pharmacology

biochemistry

The compound acts as a very selective agonist on the α 2 -adrenoceptor . It also binds to the 5-HT2B receptor as a selective agonist . In rats, guanfacine leads to an improved short-term memory by inhibiting the formation of the secondary messenger substance cAMP in the prefrontal cortex .

Mechanism of action

The cause of the antihypertensive effect is, on the one hand, the stimulation of the α 2 -adrenoceptors with the result of a reduced release of noradrenaline and the agonistic effect on the imidazoline receptors. The result is a decrease in peripheral vascular resistance, heart rate and cardiac output.

The mechanism of action of guanfacine in the treatment of ADHD is not fully understood. In rats, a dose-dependent decrease in impulsivity was found , which was assigned to an assumed support of functions in the prefrontal cortex.

Pharmacokinetics

The oral bioavailability is 80%. There is no evidence of a first pass effect . The biological half-life is 17 hours. Guanfacine is excreted through the kidneys . In the course of the biotransformation , 3-hydroxy guanfacine is formed.

history

Guanfacine was first presented in 1974 under the code name "BS 100-141" at the spring meeting of the German Pharmacological Society in Mainz as a new pharmacologically active substance. It was introduced in 1979 for the treatment of high blood pressure under the brand name Estulic by the then Sandoz subsidiary Wander . Since the drug was approved by the US Food and Drug Administration in 1986, guanfacine has also been on the market in the US for the treatment of high blood pressure. In September 2009 guanfacine was first approved in the United States for the treatment of ADHD under the trade name Intuniv. In September 2015, the drug approval in the EU followed by the European Medicines Agency .

Trade names

  • Estulic ( D , aH ), Tenex ( USA )
  • Intuniv (EU, USA, CA )

Individual evidence

  1. ↑ a b c Entry on guanfacine hydrochloride at TCI Europe, accessed on February 2, 2016.
  2. ^ NT Bello: Clinical utility of guanfacine extended release in the treatment of ADHD in children and adolescents. In: Patient preference and adherence. Volume 9, 2015, pp. 877-885. doi: 10.2147 / PPA.S73167 . PMID 26170637 , PMC 4494608 (free full text) (review).
  3. ↑ a b c K. Neumann: Second Chance for Guanfacin , October 6, 2015.
  4. ^ P. Jerie: Clinical experience with guanfacine in long-term treatment of hypertension. In: British journal of clinical pharmacology. Volume 10, Suppl 1, 1980, pp. 37S-47S. PMID 6994777 , PMC 1430120 (free full text).
  5. ↑ a b European Medicines Agency (EMA): Intuniv / guanfacine , accessed on February 3, 2016.
  6. ^ Bernard J. Lee: Clinical experience with guanfacine in 2- and 3-year-old children with Attention Deficit Hyperactivity Disorder . In: Infant Mental Health Journal . tape 18 , no. 3 , September 1997, p. 300-305 , doi : 10.1002 / (SICI) 1097-0355 (199723) 18: 33.0.CO; 2-Q ( PDF ).
  7. ↑ Amy FT Arnsten: The use of α-2A adrenergic agonists for the treatment of attention-deficit / hyperactivity disorder . In: Expert Review of Neurotherapeutics . No. 10 , October 2010, p. 1595–1605 , doi : 10.1586 / ern.10.133 , PMC 3143019 (free full text).
  8. ↑ BL Roth, J. Driscol: PDSP K i database (12 January 2011). ( Memento of the original from November 8, 2013 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. University of North Carolina at Chapel Hill and the United States National Institute of Mental Health @1@ 2Template: Webachiv / IABot / pdsp.med.unc.edu
  9. ↑ X.-P. Huang, V. Setola, PN Yadav, JA Allen, SC Rogan, BJ Hanson, C. Revankar, M. Robers, C. Doucette, BL Roth: Parallel Functional Activity Profiling Reveals Valvulopathogens Are Potent 5-Hydroxytryptamine2B Receptor Agonists: Implications for Drug Safety Assessment. In: Molecular Pharmacology. 76, 2009, p. 710. doi: 10.1124 / mol.109.058057 . PMC 2769050 (free full text).
  10. ^ BP Ramos, D. Stark, L. Verduzco, CH van Dyck, AF Arnsten: Alpha2A-adrenoceptor stimulation improves prefrontal cortical regulation of behavior through inhibition of cAMP signaling in aging animals. In: Learning & memory. Volume 13, Number 6, Nov-Dec 2006, pp. 770-776. doi: 10.1101 / lm.298006 . PMID 17101879 , PMC 1783631 (free full text).
  11. ↑ Ernst Mutschler, Monika Schäfer-Korting: drug effects. Textbook of pharmacology and toxicology. 7th edition. Wissenschaftliche Verlagsgesellschaft, Stuttgart 1996, p. 294.
  12. ↑ AB Fernando, D. Economidou, DE Theobald, MF Zou, AH Newman, M. Spoelder, D. Caprioli, M. Moreno, L. Hipólito, AT Aspinall, TW Robbins, JW Dalley: Modulation of high impulsivity and attentional performance in rats by selective direct and indirect dopaminergic and noradrenergic receptor agonists. In: Psychopharmacology. Volume 219, Number 2, January 2012, pp. 341-352. doi: 10.1007 / s00213-011-2408-z . PMID 21761147 , PMC 3249163 (free full text).
  13. ↑ JR Kiechel: Pharmacokinetics and metabolism of guanfacine in man: a review. In: British journal of clinical pharmacology. Volume 10, Suppl 1, 1980, pp. 25S-32S. PMID 6994775 , PMC 1430131 (free full text).
  14. ↑ G. Scholtysik: Inhibition of effects of accelerator nerve stimulation in cats and rabbits by BS 100-141 and guanabenz. In: Naunyn Schmiedebergs Arch. Pharmacol. Volume 282, (Suppl), 1974, p. R86. PMID 4276642
  15. ↑ Drugs.com: Shire Announces FDA Approval of Once-Daily Intuniv (guanfacine) Extended Release Tablets for the Treatment of ADHD in Children and Adolescents Aged 6 to 17 , accessed February 17, 2017.