α ₂ adrenoceptor

The α ₂ -adrenoceptors are in the central and peripheral nervous system occurring receptors , represented by epinephrine and norepinephrine are activated. They mediate their effects via inhibitory G _{i / o} proteins . Based on their pharmacological properties, they are divided into four subtypes: α _2A , α _2B , α _2C and α _2D , the α _2D subtype not occurring in mammals.

Occurrence and function

α ₂ -adrenoceptors occur in high density both pre- and postsynaptically (see synaptic gap ) in the central nervous system and in the peripheral nervous system . In the central nervous system, activation of α ₂ -adrenoceptors leads to predominantly inhibitory effects: inhibition of neurotransmitter release, analgesia , sedation , central blood pressure lowering and hypothermia . Peripheral functions include a vasoconstriction ( paradoxical clonidine -Wirkung after i. V. Administration), and a promotion of platelet aggregation a.

pharmacology

α ₂ -adrenoceptor agonists ( α2-agonists for short ) behave effectively sympatholytically via a physiologically negative feedback mechanism : " indirect sympatholytics or anti- sympathotonics ". α ₂ -receptor interaction leads to a decrease in the action potential frequency of the sympathetic part of the autonomic nervous system. They are therefore therapeutic

• used to treat arterial hypertension ( clonidine , moxonidine ) (only for therapy-resistant hypertension and in combination therapy)
• in Switzerland and the USA, clonidine is also used to treat ADHD .
• used to lower intraocular pressure in chronic wide-angle glaucoma ( clonidine , brimonidine and dipivefrin ).
• used as a centrally effective muscle relaxant ( tizanidine ) by inhibiting excitatory interneurons. Tizanidine is used clinically for centrally caused spasticity and pain-related muscle tension.
• In addition, α ₂ -adrenoceptor agonists are also used in human and veterinary medicine as sedatives and narcotics (e.g. xylazine , dexmedetomidine , medetomidine )

α ₂ -adrenoceptor ant agonists act as indirect sympathomimetics via the negative feedback mechanism mentioned above : they increase the action potential frequency of the sympathetic nervous system. Therapeutically, they are used to increase male sexual function ( yohimbine ) and as antidepressants ( mianserin , mirtazapine and idazoxan).

Pharmacological properties and function of the α ₂ -adrenoceptors

property	α 2A / D	α 2B	α 2C
Agonists	Adrenaline , noradrenaline , clonidine , moxonidine , brimonidine
Selective agonists	Guanfacine	-	-
Antagonists	RS 79948, RX821002, Yohimbin , Rauwolscin
Selective antagonists	BRL44408	ARC 239	-
function	Hypotension , sedation , analgesia , platelet aggregation	Vasoconstriction	-

Sudden discontinuation of long-term medication with α ₂ agonists can lead, among other things, to dangerously high blood pressure, tachycardia and headaches.

Signal transmission pathways at the α ₂ adrenoceptor

• Inhibition of adenylyl cyclase
• Mobilization of calcium - ion from intracellular stores
• Stimulation of the calcium influx through L-type channels
• Inhibition of calcium influx through N-type channels
• Activation of potassium channels
• Activation of the sodium / hydrogen antiport

literature

• Guimarães S, Moura D: Vascular adrenoceptors: an update . In: Pharmacol Rev . 53, No. 2, June 2001, pp. 319-56. PMID 11356987 .
• Alexander SPH, Mathie A, Peters JA: Guide to Receptors and Channels (GRAC), 4th Edition . In: Br J Pharmacol . 158 Suppl 1, November 2009, pp. S1-254. doi : 10.1111 / j.1476-5381.2009.00499.x . PMID 19883461 .

Individual evidence

1. ↑ https://www.ncbi.nlm.nih.gov/pubmed/28622977
2. ^ German Society for Cardiology - Heart and Circulatory Research: ESC Pocket Guidelines. Management of arterial hypertension. In: European Heart Journal. Volume 34, 2013, pp. 2159-2219.
3. ↑ L. Wechsler, α2- Adrenoceptor Agonists in the Treatment of ADHD, Clinic and Research 2013 ISSN  0947-8736 ; 19: 2; 98-102.
4. ↑ Peter Weber: New aspects in the pharmacotherapy of ADHD in childhood and adolescence (PDF; 338 kB). In: Pediatrics, No. 1/2007, ISSN  1424-8468 , pp. 16-21, here pp. 20-21.
5. ↑ SL Pai et al. a .: Pharmacologic and Perioperative Considerations for Antihypertensive Medications. In: Curr Clin Pharmacol. 12, 2017, pp. 1–6.
6. ↑ L. Lu, GA Ordway: Alpha2C-adrenoceptors mediate inhibition of forskolin-stimulated cAMP production in rat striatum. In: Brain research. Molecular brain research. Volume 52, Number 2, December 1997, pp. 228-234, ISSN  0169-328X . PMID 9495543 .
7. ↑ ^{a b} K. Sathishkumar, GR Ross, PR Prakash, SK Mishra: Relative contribution of intracellular and extracellular Ca2 + to alpha2-adrenoceptor-mediated contractions of ovine pulmonary artery. In: Pharmacological Research Volume 54, Number 3, September 2006, pp. 219-225, ISSN  1043-6618 . doi : 10.1016 / j.phrs.2006.05.002 . PMID 16787748 .
8. ↑ KM Chiu, TY Lin, CW Lu, SJ Wang: Inhibitory effect of glutamate release from rat cerebrocortical nerve terminals by? 2 adrenoceptor agonist dexmedetomidine. In: European Journal of Pharmacology Volume 670, Number 1, November 2011, pp. 137-147, ISSN  1879-0712 . doi : 10.1016 / j.ejphar.2011.08.012 . PMID 21914443 .
9. ↑ K. Hara, T. Yamakura, T. Sata, RA Harris: The effects of anesthetics and ethanol on alpha2 adrenoceptor subtypes expressed with G protein-coupled inwardly rectifying potassium channels in Xenopus oocytes. In: Anesthesia and analgesia. Volume 101, Number 5, November 2005, pp. 1381-1388, ISSN  0003-2999 . doi : 10.1213 / 01.ANE.0000180190.05238.D5 . PMID 16243998 .