Amezinium metilsulfate

Amezinium metilsulfate (INNTooltip International Nonproprietary Name, sold under the brand name Regulton, is a sympathomimetic drug which is widely used in the treatment of orthostatic hypotension in Japan.^[1]^[2]^[3]^[4]

AHFS/Drugs.comInternational Drug Names

Routes of
administrationOral

ATC code

C01CA25 (WHO)

Legal status

In general: ℞ (Prescription only)

Quick facts Clinical data, AHFS/Drugs.com ...

Amezinium metilsulfate
Clinical data

AHFS/Drugs.com	International Drug Names
Routes of administration	Oral
ATC code	C01CA25 (WHO)
Legal status
Legal status	In general: ℞ (Prescription only)
Identifiers
IUPAC name 6-Methoxy-1-phenylpyridazin-1-ium-4-amine; methyl sulfate
CAS Number	30578-37-1^N
PubChem CID	71926
ChemSpider	64937^Y
UNII	03NR868ICX
KEGG	D01304^Y
ChEBI	CHEBI:31201
ChEMBL	ChEMBL2106667^N
CompTox Dashboard (EPA)	DTXSID00184657
ECHA InfoCard	100.045.665
Chemical and physical data
Formula	C₁₂H₁₅N₃O₅S
Molar mass	313.33 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES COC1=[N+](N=CC(=C1)N)C2=CC=CC=C2.COS(=O)(=O)[O-]
InChI InChI=1S/C11H11N3O.CH4O4S/c1-15-11-7-9(12)8-13-14(11)10-5-3-2-4-6-10;1-5-6(2,3)4/h2-8,12H,1H3;1H3,(H,2,3,4)^Y Key:ZEASXVYVFFXULL-UHFFFAOYSA-N^Y
^NY (what is this?) (verify)

Pharmacology

Pharmacodynamics

Amezinium metilsulfate has a unique mechanism of action of acting as a dual monoamine oxidase inhibitor (MAOI) and norepinephrine reuptake inhibitor (NRI).^[3]^[2]^[4]

Chemistry

Synthesis

This drug is made from 2-butyne-1,4-diol starting material with chloridazon [de] as an intermediate.

The halogenation of 2-butyne-1,4-diol (1) with chlorine gives mucochloric acid (2). Treatment with phenylhydrazine (3) gives 1-phenyl-4,5-dichloro-6-pyridazone (4). Addition of ammonia leads to chloridazon (5). Catalytic hydrogenation yields 5-amino-2-phenylpyridazin-3-one (6). Alkylation with dimethyl sulfate completes the synthesis of amezinium metisulfate (7).

References

[1]
"Delving into the Latest Updates on Amezinium Metilsulfate with Synapse". Synapse. 28 October 2025. Retrieved 13 March 2026.
[2]
Deftereos SN, Dodou E, Andronis C, Persidis A (July 2012). "From depression to neurodegeneration and heart failure: re-examining the potential of MAO inhibitors". Expert Rev Clin Pharmacol. 5 (4): 413–425. doi:10.1586/ecp.12.29. PMID 22943121. Amezinium metilsulfate (risumic, supratonin, amezinin and ryzmilate) is an indirectly acting sympathomimetic drug available in Japan, which reversibly inhibits intraneuronal MAO-A and MAO-B, as well as the reuptake of NE at postganglionic sympathetic terminals [120,121]. Amezinium is indicated for the treatment of essential hypotension, orthostatic hypotension and hypotension during dialysis [208].
[3]
Oldenburg O, Kribben A, Baumgart D, Philipp T, Erbel R, Cohen MV (December 2002). "Treatment of orthostatic hypotension". Curr Opin Pharmacol. 2 (6): 740–747. doi:10.1016/s1471-4892(02)00213-8. PMID 12482740. Amezinium metilsulfate is one of the most popular drugs in Japan for the treatment of OH. It has a unique mechanism of vasoconstriction. The drug inhibits monoamine oxidase (MAO) activity and norepinephrine (noradrenaline) uptake, and, therefore, enhances norepinephrine activity resulting in an increase in blood pressure [59]. Amezinium is especially recommended [60,61] in selected patients with asympathotonic (deficiency of sympathetic stimulation) OH [62••].
[4]
Kita K, Hirayama K (July 1988). "Treatment of neurogenic orthostatic hypotension with amezinium metilsulfate, a new indirect sympathomimetic drug". Neurology. 38 (7): 1095–1099. doi:10.1212/wnl.38.7.1095. PMID 3386828.
[5]
Unterhalt B (1981). "Amezinium metilsulfate". Drugs of the Future. 6 (4): 207. doi:10.1358/dof.1981.006.04.199346.
[6]
Reicheneder F, Burger TF, König H, Kropp R, Lietz H, Thyes M, Wiersdorff WW (1981). "Amezinium. Synthesis and radioactive labelling". Arzneimittel-Forschung. 31 (9a): 1529–1533. PMID 7197967.
[7]
Beljean M, Pays M. "Heterocyclic hydrazines and hydrazones. II. Synthesis of hydrazino derivatives and of hydrazones in the thiazolo[4,5-d]pyridazin-7-ones". Bulletin de la Société Chimique de France. 12 (2): 3324–3330.