This looks interesting:
Pharm Res 1997 Mar;14(3):325-328 Delivery of loperamide across
the blood-brain barrier with polysorbate 80-coated
polybutylcyanoacrylate nanoparticles.
Alyautdin RN, Petrov VE, Langer K, Berthold A, Kharkevich DA,
Kreuter J
Department of Pharmacology, Sechenov Medical Academy, Moscow,
Russia.
PURPOSE: The possibility of using polysorbate 80-coated
nanoparticles for the delivery of the water insoluble opioid
agonist loperamide across the blood-brain barrier was
investigated. The analgesic effect after i.v. injection of the
preparations was used to indicate drug transport through this
barrier. METHODS: Loperamide was incorporated into PBCA
nanoparticles. Drug-containing nanoparticles were coated with
polysorbate 80 and injected intravenously into mice. Analgesia
was then measured by the tail-flick test. RESULTS: Intravenous
injection of the particulate formulation resulted in a long and
significant analgesic effect. A polysorbate 80 loperamide
solution induced a much less pronounced and very short analgesia.
Uncoated nanoparticles loaded with loperamide were unable to
produce analgesia. CONCLUSIONS: Polysorbate 80-coated PBCA
nanoparticles loaded with loperamide enabled the transport of
loperamide to the brain.
PMID: 9098875, UI: 97253432
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Life Sci 1983;33 Suppl 1:315-318 Loperamide: evidence of
interaction with mu and delta opioid receptors.
Giagnoni G, Casiraghi L, Senini R, Revel L, Parolaro D, Sala M,
Gori E
Loperamide was tested on electrically-evoked contractions using a
series of "in vitro" isolated preparations, in comparison with
morphine, met-enkephalin, beta-endorphin, ethylketocyclazocine
used as representative agonists of mu, delta, epsilon, kappa
receptors respectively. The IC50 of loperamide on myenteric
plexus longitudinal muscle of guinea pig ileum was found to be
1.90 X 10(-7)M and equal to that of morphine. The IC50 on mouse
vas deferens was found to be 13.02 X 10(-7)M. In this tissue,
loperamide resulted as active as morphine, but 54 times less
active than met-enkephalin (IC50 0.24 X 10(-7)M). On the rat vas
deferens where, as expected, beta-endorphin was strongly active
(IC50 1.38 X 10(-7)M), morphine exerted a stimulatory action
within the range 10(-5)M-10(-4)M and loperamide was only poorly
depressive. The Ke value of naloxone, a specific mu receptor
antagonist, against loperamide in the guinea pig ileum was 3.83
nM, and in the mouse vas deferens was 82.87 nM indicating that
loperamide in the guinea pig ileum acts on mu receptors while in
the mouse vas deferens on another opiate receptor.
PMID: 6319884, UI: 84116593
