グアネチジン 化学特性,用途語,生産方法
効能
血圧降下薬, 縮瞳薬, ノルアドレナリン有利抑制薬
説明
Guanethidine is used for severe hypertension when the use of the more generally
accepted drugs turns out to be unsuccessful. It is a powerful, long-lasting antihypertensive
drug; however, it affects a patient’s blood pressure only in the orthostatic position, and not
when lying down.
Guanethidine is a very powerful and long-lasting drug, and its action often lasts 2–3
days after its use has been stopped.
使用
Guanethidine is used for severe hypertension, where use of more universally accepted
drugs is not successful. It is a very powerful and long-lasting drug, and its effects last for
2–3 days after using it.
使用
Antihypertensive.
定義
ChEBI: A member of the class of guanidines in which one of the hydrogens of the amino group has been replaced by a 2-azocan-1-ylethyl group.
生物学の機能
Guanethidine (Ismelin) is a powerful antihypertensive
agent that is quite effective in the treatment of moderate
to severe hypertension. It is most frequently used in
the treatment of severe hypertension that is resistant to
other agents.
Guanethidine exerts its effects at peripheral sympathetic
nerve endings following its active transport into the
nerve varicosities by the neuronal amine transport system.
This is the same uptake system that transports norepinephrine
into the varicosity).The accumulation
of guanethidine in adrenergic neurons,
through an as yet unexplained mechanism, disrupts the
process by which action potentials trigger the release of
stored norepinephrine and other cotransmitters from
nerve terminals. It is this action of guanethidine that is
primarily responsible for its antihypertensive properties.
Parasympathetic function is not altered, a fact that
distinguishes guanethidine from the ganglionic blocking
agent.
Guanethidine is suitable for oral use, and this is its
usual route of administration. However, absorption
from the gastrointestinal tract is variable. The half-life
of guanethidine is 5 days, with about one-seventh of the
total administered dose eliminated per day. The slow
elimination contributes to the cumulative and prolonged
effects of the drug.
Guanethidine reduces blood pressure by its ability
to diminish vascular tone; both the arterial and venous
sides of the circulatory system are involved. The resulting
venous pooling contributes to orthostatic hypotension,
a prominent feature of guanethidine treatment.
The reduction in blood pressure is more prominent
when the patient is standing than recumbent.
一般的な説明
Guanethidine or guanethidinesulfate [C
10H
22N
4·H
2SO
4].
作用機序
Unlike adrenoblockers, guanethidine does not act on effector cells. It acts on branched
ends of sympathetic peripheral nerve fibers and permeates into the neuron by the same
mechanism of reverse uptake that returns norepinephrine from the synaptic cleft to neuron endings. Inside the neuron, guanethidine accumulates and competes with norepinephrine for storage space as granules. With an increase in guanethidine concentration,
norepinephrine is replaced and thus the quantity of neurotransmitters capable of being
released is reduced. In response to stimulation, the nerve may release guanethidine,
which, however, is not an adrenergic receptor stimulant. In addition to this disturbance
and the presence of stores of catecholamines in adrenergic nerve endings, guanethidine
also acts on the stores of catecholamines in organs such as the heart, spleen, and aorta.Since it does not pass through the blood–brain barrier, it does not act on the central sympathetic neurons.
副作用
Guanethidine may aggravate congestive heart failure
or actually precipitate failure in patients with marginal
cardiac reserve, owing to its ability to produce vascular
volume expansion, edema, and a reduced
effectiveness of sympathetic cardiac stimulation.
Guanethidine is contraindicated in patients with
pheochromocytoma because the drug may release catecholamines
from the tumor. The concomitant use of
monoamine oxidase (MAO) inhibitors and guanethidine
is also to be avoided, since this combined drug
treatment eliminates two of the principal mechanisms
for terminating the actions of the catecholamines and
certain other adrenomimetic drugs, that is, biotransformation
and neuronal uptake. Dangerously high concentrations
of catecholamines at receptor sites are possible.
合成
Guanethidine, |?-(1-azacyclooctyl)ethylguanidine (12.3.4), is synthesized
in the following straightforward manner. Azocine is alkylated by chloracetonitrile, which
forms 1-azocinylacetonitrile (12.3.2), which is reduced by lithium aluminum hydride into
1-(2-aminoethyl)azocine (12.3.3). Reacting this with S-methylthiourea gives guanethidine
(12.3.4) [77¨C79].
グアネチジン 上流と下流の製品情報
原材料
準備製品