I'm certain that we've posted this before, but.... just ran across it again, and felt that I should post it. I'll check to see if any new patents have issued lately. This is from the SPO, 6/19/98.....
A U.S. patent application, filed solely by the Company, has been issued
covering the composition of matter for a series of synthetic histamine H(3)
receptor antagonist compounds, which is due to expire in 2015. Several
additional U.S. patent applications and their corresponding foreign applications
for additional series of histamine H(3) receptor antagonists and one series of
histamine H(3) receptor agonist compounds, their methods of medical use and
pharmaceutical compositions, are pending. No assurance can be given that any
claims relating to these products and methods will be issued.
Also, I've been continuing to poke through Medline. The only other company that I can find with an active program in H3-receptor antagonists and agonists is Schering-Plough. That program looks to be a significant effort, if Medline citations are a gauge.
While we focus on the antagonists, there's much that can be learned from looking at the agonist literature. And, of course, GLIA has their own agonist program too......
J Pharmacol Exp Ther 1998 Oct;287(1):43-50
Sch 50971, an orally active histamine H3 receptor agonist, inhibits central
neurogenic vascular inflammation and produces sedation in the guinea pig.
McLeod RL, Aslanian R, del Prado M, Duffy R, Egan RW, Kreutner W, McQuade R, Hey JA
Schering-Plough Research Institute, Kenilworth, New Jersey, USA.
We studied the actions of Sch 50971, a novel histamine H3 receptor agonist, in an experimental neurogenic model of migraine
and characterized its sedative and respiratory actions. Sch 50971 (i.v. and p.o) inhibited plasma protein extravasation in the
dura mater of guinea pigs after electrical stimulation of the trigeminal ganglia. The minimum effective doses of Sch 50971 were
3.0 mg/kg i.v. and 10 mg/kg p.o., which produced a 40% and 42% decrease in plasma protein extravasation, respectively. The
effects of Sch 50971 (3.0 mg/kg i.v. ) were blocked by the histamine H3 antagonist thioperamide (3.0 mg/kg i.v.). The
5-HT1D agonist, sumatriptan (0.3 mg/kg i.v.), and the histamine H3 agonist, (R)-alpha-methylhistamine (0.3 mg/kg), also
inhibited plasma extravasation by 40 and 46%. In sedation studies, Sch 50971 (1-100 mg/kg p.o.) potentiated
pentobarbital-induced sleep. The ED40 min for Sch 50971, the benzodiazepines triazolam and diazepam, the histamine H1
antagonist diphenhydramine and the H3 receptor agonist (R)-alpha-methylhistamine were 7.0, 0.5, 2.3, 14.1 and 23.4 mg/kg
p. o., respectively. The sedative effects of oral Sch 50971 was blocked by thioperamide (10 microgram i.c.v.). The sedative
activity of Sch 50971 was also examined using EEG activity, locomotor activity and sleep. In conscious guinea pigs, Sch 50971
(10 mg/kg p.o.) depressed locomotor activity, increased total sleep time and produced EEG patterns consistent with
physiological sleep. Sch 50971 decreased beta wave activity but had no effects on delta wave activity, theta activity or alpha
wave activity. In contrast, triazolam (1.0 mg/kg p. o.) depressed delta and theta wave activity and produced large increases in
alpha and beta wave activity. In conclusion, Sch 50971 is an orally active, potent and selective agonist of histamine H3
receptors that may act to ameliorate the sequelae of migraine headaches, where activation of histamine H3 receptors may be
beneficial. Sch 50971 also decreases motor activity and promotes EEG activity consistent with physiological sleep. |
