Biomaterial Database

The hypotensive activity and side effects of methyldopa, clonidine, and guanfacine. 1984

P A van Zwieten, and M J Thoolen, and P B Timmermans

Clonidine (Catapres, Catapresan), guanfacine (Estulic), and methyldopa (Aldomet) are the prototypes of centrally acting antihypertensive drugs. Clonidine and guanfacine are lipophilic drugs that readily penetrate into the brain, where they stimulate alpha-adrenergic receptors in the pontomedullary region. The stimulation of these central alpha-adrenergic receptors has been shown to activate an inhibiting neuron, which causes a reduction of peripheral sympathetic tone and a subsequent fall in arterial blood pressure and heart rate. Both a centrally initiated reduction of vagus reflex activity and the activation of presynaptic alpha 2-adrenergic blocking agents in the heart may contribute to the bradycardia. Studies indicate that methyldopa also penetrates into the brain, where it is converted into alpha-methylnorepinephrine. This amine may stimulate the same central alpha-adrenergic receptors as those activated by clonidine, which will result in a hypotensive effect. Possibly, alpha-methyldopamine might also play a role. Accordingly, the modes of action of clonidine and alpha-methyldopa probably are very similar at a basic level. The central adrenergic receptors probably are located postsynaptically. Their receptor demand corresponds more closely to that of the alpha 2-subtype. Central alpha 1-adrenergic receptors might possibly play a part in the modulation of vagally induced baroreflex bradycardia. A discussion on the pharmacological basis of the side effects of the centrally acting antihypertensives has been limited to those adverse reactions that are somehow related to alpha-adrenergic receptors. Sedation, a common side effect, appears to be mediated by central alpha 2-adrenergic receptors, at least in animal models.(ABSTRACT TRUNCATED AT 250 WORDS)

UI	MeSH Term	Description	Entries
D008750	Methyldopa	An alpha-2 adrenergic agonist that has both central and peripheral nervous system effects. Its primary clinical use is as an antihypertensive agent.	Methyldopate,alpha-Methyldopa,Aldomet,Alphamethyldopa,Apo-Methyldopa,Dopamet,Dopegit,Dopegyt,Dopergit,Hydopa,Meldopa,Nu-Medopa,Sembrina,alpha-Methyl-L-Dopa,Apo Methyldopa,Nu Medopa,alpha Methyl L Dopa,alpha Methyldopa
D009638	Norepinephrine	Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic.	Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D010648	Phenylacetates	Derivatives of phenylacetic acid. Included under this heading are a variety of acid forms, salts, esters, and amides that contain the benzeneacetic acid structure. Note that this class of compounds should not be confused with derivatives of phenyl acetate, which contain the PHENOL ester of ACETIC ACID.	Benzeneacetates,Benzeneacetic Acids,Phenylacetic Acids,Acids, Benzeneacetic,Acids, Phenylacetic
D011942	Receptors, Adrenergic, alpha	One of the two major pharmacological subdivisions of adrenergic receptors that were originally defined by the relative potencies of various adrenergic compounds. The alpha receptors were initially described as excitatory receptors that post-junctionally stimulate SMOOTH MUSCLE contraction. However, further analysis has revealed a more complex picture involving several alpha receptor subtypes and their involvement in feedback regulation.	Adrenergic alpha-Receptor,Adrenergic alpha-Receptors,Receptors, alpha-Adrenergic,alpha-Adrenergic Receptor,alpha-Adrenergic Receptors,Receptor, Adrenergic, alpha,Adrenergic alpha Receptor,Adrenergic alpha Receptors,Receptor, alpha-Adrenergic,Receptors, alpha Adrenergic,alpha Adrenergic Receptor,alpha Adrenergic Receptors,alpha-Receptor, Adrenergic,alpha-Receptors, Adrenergic
D001794	Blood Pressure	PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.	Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D001919	Bradycardia	Cardiac arrhythmias that are characterized by excessively slow HEART RATE, usually below 50 beats per minute in human adults. They can be classified broadly into SINOATRIAL NODE dysfunction and ATRIOVENTRICULAR BLOCK.	Bradyarrhythmia,Bradyarrhythmias,Bradycardias
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D003000	Clonidine	An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION.	Catapres,Catapresan,Catapressan,Chlophazolin,Clofelin,Clofenil,Clonidine Dihydrochloride,Clonidine Hydrochloride,Clonidine Monohydrobromide,Clonidine Monohydrochloride,Clopheline,Dixarit,Gemiton,Hemiton,Isoglaucon,Klofelin,Klofenil,M-5041T,ST-155,Dihydrochloride, Clonidine,Hydrochloride, Clonidine,M 5041T,M5041T,Monohydrobromide, Clonidine,Monohydrochloride, Clonidine,ST 155,ST155
D006146	Guanidines	A family of iminourea derivatives. The parent compound has been isolated from mushrooms, corn germ, rice hulls, mussels, earthworms, and turnip juice. Derivatives may have antiviral and antifungal properties.
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man