Tiamenidine

Last updated
Tiamenidine
Tiamenidine.svg
Clinical data
Trade names Sundralen, Symcorad, Symcor
ATC code
Pharmacokinetic data
Elimination half-life 2.3–5 hours [1]
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C8H10ClN3S
Molar mass 215.70 g·mol−1
3D model (JSmol)
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Tiamenidine (BAN, USAN, INN, also known as thiamenidine, Hoe 440) is an imidazoline compound that shares many of the pharmacological properties of clonidine. It acts as a centrally-acting α1 and α2 adrenergic receptor antagonist (with IC50 4.85 μM and 0.0091 μM, respectively). [2] In hypertensive volunteers, like clonidine, it significantly increased sinus node recovery time and lowered cardiac output. [3] It was marketed (as tiamenidine hydrochloride) by Sanofi-Aventis [4] under the brand name Sundralen [5] for the management of essential hypertension. [6]

Contents

Synthesis

Tiamenidine synthesis: Tiamenidine-synthesis.svg
Tiamenidine synthesis:

Reaction of thiourea 1 with methyl iodide gives the corresponding S-methyl analogue (2), followed by heating with ethylenediamine, completes the synthesis of tiamenidine (3).

See also

Related Research Articles

Beta blocker class of medications that are particularly used to manage cardiac arrhythmias, and to protect the heart from a second heart attack after a first heart attack

Beta blockers are a class of medications that are predominantly used to manage abnormal heart rhythms, and to protect the heart from a second heart attack after a first heart attack. They are also widely used to treat high blood pressure (hypertension), although they are no longer the first choice for initial treatment of most patients.

Propranolol beta blocker drug

Propranolol, sold under the brand name Inderal among others, is a medication of the beta blocker class. It is used to treat high blood pressure, a number of types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, performance anxiety, and essential tremors. It is used to prevent migraine headaches, and to prevent further heart problems in those with angina or previous heart attacks. It can be taken by mouth or by injection into a vein. The formulation that is taken by mouth comes in short-acting and long-acting versions. Propranolol appears in the blood after 30 minutes and has a maximum effect between 60 and 90 minutes when taken by mouth.

Clonidine chemical compound

Clonidine, sold as the brand name Catapres among others, is a medication used to treat high blood pressure, attention deficit hyperactivity disorder, drug withdrawal, menopausal flushing, diarrhea, and certain pain conditions. It is used by mouth, by injection, or as a skin patch. Onset of action is typically within an hour with the effects on blood pressure lasting for up to eight hours.

Antihypertensives are a class of drugs that are used to treat hypertension. Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34%, of ischaemic heart disease by 21%, and reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease. There are many classes of antihypertensives, which lower blood pressure by different means. Among the most important and most widely used medications are thiazide diuretics, calcium channel blockers, ACE inhibitors, angiotensin II receptor antagonists (ARBs), and beta blockers.

A parasympathomimetic drug, sometimes called a cholinomimetic drug or cholinergic receptor stimulating agent, is a substance that stimulates the parasympathetic nervous system (PSNS). These chemicals are also called cholinergic drugs because acetylcholine (ACh) is the neurotransmitter used by the PSNS. Chemicals in this family can act either directly by stimulating the nicotinic or muscarinic receptors, or indirectly by inhibiting cholinesterase, promoting acetylcholine release, or other mechanisms.

Oxymetazoline a topical decongestant

Oxymetazoline is a selective α1 adrenergic receptor agonist and α2 adrenergic receptor partial agonist. It is a topical decongestant, used in the form of oxymetazoline hydrochloride. It was developed from xylometazoline at E. Merck Darmstadt by Fruhstorfer in 1961. Oxymetazoline is generally available as a nasal spray.

Xylazine chemical compound

Xylazine is an analogue of clonidine and an agonist at the α2 class of adrenergic receptor. It is used for sedation, anesthesia, muscle relaxation, and analgesia in animals such as horses, cattle and other non-human mammals. Veterinarians also use xylazine as an emetic, especially in cats.

Prazosin chemical compound

Prazosin is a medication primarily used to treat high blood pressure, symptoms of an enlarged prostate, and posttraumatic stress disorder (PTSD). It is a less preferred treatment of high blood pressure. Other uses may include heart failure and Raynaud syndrome. It is taken by mouth.

Alpha-1 blockers constitute a variety of drugs that block the effect of alpha-1-adrenergic receptors. They are mainly used to treat benign prostatic hyperplasia (BPH), hypertension and post-traumatic stress disorder. Alpha-1 adrenergic receptors occur in vascular smooth muscle, the central nervous system, and other tissues. When alpha blockers bind to these receptors in vascular smooth muscle, they cause vasodilation.

Moxonidine chemical compound

Moxonidine (INN) is a new-generation alpha-2/imidazoline receptor agonist antihypertensive drug licensed for the treatment of mild to moderate essential hypertension. It may have a role when thiazides, beta-blockers, ACE inhibitors, and calcium channel blockers are not appropriate or have failed to control blood pressure. In addition, it demonstrates favourable effects on parameters of the insulin resistance syndrome, apparently independent of blood pressure reduction. It is also a growth hormone releaser. It is manufactured by Solvay Pharmaceuticals under the brand name Physiotens & Moxon.

Labetalol chemical compound

Labetalol is a medication used to treat high blood pressure and in long term management of angina. This includes essential hypertension, hypertensive emergencies, and hypertension of pregnancy. In essential hypertension it is generally less preferred than a number of other blood pressure medications. It can be given by mouth or by injection into a vein.

The alpha-2 (α2) adrenergic receptor is a G protein-coupled receptor (GPCR) associated with the Gi heterotrimeric G-protein. It consists of three highly homologous subtypes, including α2A-, α2B-, and α2C-adrenergic. Some species other than humans express a fourth α2D-adrenergic receptor as well. Catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) signal through the α2-adrenergic receptor in the central and peripheral nervous systems.

Rilmenidine chemical compound

Rilmenidine is a prescription medication for the treatment of hypertension. It is marketed under the brand names Albarel, Hyperium, Iterium and Tenaxum.

Alpha-adrenergic agonist Drugs that selectively bind to and activate alpha adrenergic receptors.

Adrenergic alpha-agonists are a class of sympathomimetic agents that selectively stimulates alpha adrenergic receptors. The alpha-adrenergic receptor has two subclasses α1 and α2. Alpha 2 receptors are associated with sympatholytic properties. Alpha-adrenergic agonists have the opposite function of alpha blockers. Alpha adrenoreceptor ligands mimic the action of epinephrine and norepinephrine signaling in the heart, smooth muscle and central nervous system, with norepinephrine being the highest affinity. The activation of α1 stimulates the membrane bound enzyme phospholipase C, and activation of α2 inhibits the enzyme adenylate cyclase. Inactivation of adenylate cyclase in turn leads to the inactivation of the secondary messenger cyclic adenosine monophosphate and induces smooth muscle and blood vessel constriction.

Adrenergic antagonist drug that binds to but do not activate adrenergic receptors

An adrenergic antagonist is a drug that inhibits the function of adrenergic receptors. There are five adrenergic receptors, which are divided into two groups. The first group of receptors are the beta (β) adrenergic receptors. There are β1, β2, and β3 receptors. The second group contains the alpha (α) adrenoreceptors. There are only α1 and α2 receptors. Adrenergic receptors are located near the heart, kidneys, lungs, and gastrointestinal tract. There are also α-adreno receptors that are located on vascular smooth muscle.

A sympatholytic drug is a medication that opposes the downstream effects of postganglionic nerve firing in effector organs innervated by the sympathetic nervous system (SNS). They are indicated for various functions; for example, they may be used as antihypertensives. They are also used to treat anxiety, such as generalized anxiety disorder, panic disorder and PTSD.

Dezocine chemical compound

Dezocine is a marketed opioid analgesic of the benzomorphan group. First synthesized in 1970, it acts as a modulator of mu-, delta-, and kappa-opioid receptors. Dezocine is a mixed agonist/antagonist of opioid receptors. It is related to other benzomorphans such as pentazocine, with a similar profile of effects that include analgesia and euphoria. Unlike many other benzomorphans however, it is a silent antagonist of the κ-opioid receptor, and in accordance, does not produce side effects such as dysphoria or hallucinations at any dose.

Alpha blocker pharmaceutical drugs, neutral antagonist of alpha-adrenergic receptors

Alpha-blockers, also known as α-blockers or α-adrenoreceptor antagonists, are a class of pharmacological agents that act as antagonists on α-adrenergic receptors (α-adrenoceptors).

Arotinolol is a medication in the class of mixed alpha/beta blockers. It also acts as a β3 receptor agonist. A 1979 publication suggests arotinolol as having first been described in the scientific literature by Sumitomo Chemical as "β-adrenergic blocking, antiarrhythmic compound S-596".

Discovery and development of beta-blockers

β adrenergic receptor antagonists were initially developed in the 1960s, for the treatment of angina pectoris but are now also used for hypertension, congestive heart failure and certain arrhythmias. In the 1950s, dichloroisoproterenol (DCI) was discovered to be a β-antagonist that blocked the effects of sympathomimetic amines on bronchodilation, uterine relaxation and heart stimulation. Although DCI had no clinical utility, a change in the compound did provide a clinical candidate, pronethalol, which was introduced in 1962.

References

  1. Eckert HG, Baudner S, Weimer KE, Wissmann H (1981). "Determination of tiamenidine in biological specimens by radioimmunoassay". Arzneimittel-Forschung. 31 (3): 419–24. PMID   7194666.
  2. Timmermans PB, de Jonge A, Thoolen MJ, Wilffert B, Batink H, van Zwieten PA (April 1984). "Quantitative relationships between alpha-adrenergic activity and binding affinity of alpha-adrenoceptor agonists and antagonists". Journal of Medicinal Chemistry. 27 (4): 495–503. doi:10.1021/jm00370a011. PMID   6142954.
  3. Roden DM, Nadeau JH, Primm RK (June 1988). "Electrophysiologic and hemodynamic effects of chronic oral therapy with the alpha 2-agonists clonidine and tiamenidine in hypertensive volunteers". Clinical Pharmacology and Therapeutics. 43 (6): 648–54. doi:10.1038/clpt.1988.90. PMID   2897889.
  4. "Pharmaceutical and healthcare online databases. Tiamenidine Hydrochloride". Drugs-About.com. Retrieved 30 November 2015.
  5. Ganten D, Mulrow PJ, eds. (2013). Pharmacology of Antihypertensive Therapeutics (1st ed.). [S.l.]: Springer-Verlag Berlin Heidelberg. p. 880. ISBN   978-3-642-74211-8.
  6. Zamboulis C, Hossmann V, Dollery CT, Eckert H (October 1979). "Tiamenidine, a centrally acting antihypertensive drug in essential hypertension [proceedings]". British Journal of Clinical Pharmacology. 8 (4): 390P. doi:10.1111/j.1365-2125.1979.tb04737.x. PMID   508528.
  7. US 3758476,issued 1973