Xylamidine is a drug which acts as an
antagonist at the
5HT2Areceptor, and to a lesser extent at the 5HT1A receptor. It does not cross the
blood–brain barrier, which makes it useful for blocking peripheral serotonergic responses like
cardiovascular[1][2] and
gastrointestinal effects,[3] without producing the central effects of 5HT2A blockade such as
sedation, or interfering with the central actions of 5HT2A agonists.[4]
Synthesis
Xylamidine is an
amidine which serves as a serotonin inhibitor. This agent is prepared by alkylation of
3-methoxyphenol (m-methoxyphenol) with α-
chloropropionitrile, KI and potassium carbonate in
MEK to give #, which is in turn reduced with
lithium aluminium hydride to give the primary amine #. When # is treated with m-
tolylacetonitrile in the presence of anhydrous HCl, the synthesis is completed. Alternately, one can react primary amine # with m-
tolylacetamidine under acid catalysis to produce xylamidine.
References
^Fuller RW, Kurz KD, Mason NR, Cohen ML (June 1986). "Antagonism of a peripheral vascular but not an apparently central serotonergic response by xylamidine and BW 501C67". European Journal of Pharmacology. 125 (1): 71–7.
doi:
10.1016/0014-2999(86)90084-1.
PMID3732393.
^Dedeoğlu A, Fisher LA (December 1991). "Central and peripheral injections of the 5-HT2 agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, modify cardiovascular function through different mechanisms". The Journal of Pharmacology and Experimental Therapeutics. 259 (3): 1027–34.
PMID1762059.
^Baker BJ, Duggan JP, Barber DJ, Booth DA (May 1988). "Effects of dl-fenfluramine and xylamidine on gastric emptying of maintenance diet in freely feeding rats". European Journal of Pharmacology. 150 (1–2): 137–42.
doi:
10.1016/0014-2999(88)90759-5.
PMID3402534.
^Dave KD, Quinn JL, Harvey JA, Aloyo VJ (March 2004). "Role of central 5-HT2 receptors in mediating head bobs and body shakes in the rabbit". Pharmacology, Biochemistry, and Behavior. 77 (3): 623–9.
doi:
10.1016/j.pbb.2003.12.017.
PMID15006475.
S2CID25205829.
Xylamidine is a drug which acts as an
antagonist at the
5HT2Areceptor, and to a lesser extent at the 5HT1A receptor. It does not cross the
blood–brain barrier, which makes it useful for blocking peripheral serotonergic responses like
cardiovascular[1][2] and
gastrointestinal effects,[3] without producing the central effects of 5HT2A blockade such as
sedation, or interfering with the central actions of 5HT2A agonists.[4]
Synthesis
Xylamidine is an
amidine which serves as a serotonin inhibitor. This agent is prepared by alkylation of
3-methoxyphenol (m-methoxyphenol) with α-
chloropropionitrile, KI and potassium carbonate in
MEK to give #, which is in turn reduced with
lithium aluminium hydride to give the primary amine #. When # is treated with m-
tolylacetonitrile in the presence of anhydrous HCl, the synthesis is completed. Alternately, one can react primary amine # with m-
tolylacetamidine under acid catalysis to produce xylamidine.
References
^Fuller RW, Kurz KD, Mason NR, Cohen ML (June 1986). "Antagonism of a peripheral vascular but not an apparently central serotonergic response by xylamidine and BW 501C67". European Journal of Pharmacology. 125 (1): 71–7.
doi:
10.1016/0014-2999(86)90084-1.
PMID3732393.
^Dedeoğlu A, Fisher LA (December 1991). "Central and peripheral injections of the 5-HT2 agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, modify cardiovascular function through different mechanisms". The Journal of Pharmacology and Experimental Therapeutics. 259 (3): 1027–34.
PMID1762059.
^Baker BJ, Duggan JP, Barber DJ, Booth DA (May 1988). "Effects of dl-fenfluramine and xylamidine on gastric emptying of maintenance diet in freely feeding rats". European Journal of Pharmacology. 150 (1–2): 137–42.
doi:
10.1016/0014-2999(88)90759-5.
PMID3402534.
^Dave KD, Quinn JL, Harvey JA, Aloyo VJ (March 2004). "Role of central 5-HT2 receptors in mediating head bobs and body shakes in the rabbit". Pharmacology, Biochemistry, and Behavior. 77 (3): 623–9.
doi:
10.1016/j.pbb.2003.12.017.
PMID15006475.
S2CID25205829.