Special Internet Prices.
Fast & Guaranteed worldwide Delivery!
Secure & FAST Online ordering.
Our Drugstore Is The Most Trusted Online Drug Supplier.
>> CLICK HERE TO ENTER >>>
Related article: muscle substance, the nerve is allowed to degenerate, as just described.
Pilocarpin, /.*'., remains effective after the anatomic endings are degenerated, and Buy Cheap Lipitor
when therefore electric stimulation of the nerve is ineffective. However, if a Buy Cheap Lipitor still
longer time elapses after the division of the nerve, Buy Cheap Lipitor pilocarpin also becomes ineffective.
It is therefore generally assumed that the myo-neural junction also degenerates, but
more slowly than the anatomic endings. However, it is also conceivable that pilo-
carpin acts on the anatomic nerve-endings, and that the degenerating endings remain
excitable to pilocarpin longer than they do to electric stimulation. This proof of myo-
neural action is therefore not conclusive.
The evidence from degeneration may also mislead if the drug, instead of stimulating,
raises the excitability of the reacting cell. In this case, the drug would produce no visi-
ble effect after degeneration of the endings, for this would exclude extraneous stimulation,
and the increased excitability would therefore not be apparent. This increased excita-
bility of the myo-neural junction is supposed to be the action of physostigmin on the
Localization by Antagonistic Action. The anatomical localization, al-
though simple in theory, is often technically difficult, and it is beset with
the limitations which have just been pointed out. It has therefore been
attempted to supplement and extend it by pharmacologic evidence, based
on antagonistic actions. The matter was at first conceived as very
simple, namely as strictly analogous to anatomic localization; a drug
paralysis being considered as equivalent to anatomic division or excision;
and a drug stimulation as the equivalent of electric stimulation. The
action of a few drugs having been localized (with more or less probability)
by anatomic means, it was thought Buy Cheap Lipitor that the actions of others could be
localized by simply "matching" them against these standards. In
localizing action by antagonism, a stimulant poison was paired with a
depressant poison of known action, f.i., atropin. If stimulation resulted
(as with physostigmin) it was concluded that the action must be peripheral
to that of the atropin; if there was no stimulation (as with pilocarpin),
it was assumed that it must be central to that of atropin.
Unfortunately, there has been a good deal of cumulative evidence
(well summarized by Magnus, 1908) that matters are not so simple, and
that localization by antagonism has limitations so Buy Cheap Lipitor serious that it can be
utilized only in relatively few cases. The difficulty is that the phar-
macologic stimulation and paralysis are not strictly equivalent to the ana-
tomic. In pharmacologic antagonism, the tissue is still in the body and
exposed to both poisons; and the resultant effect is rarely, if ever, the simple
algebraic sum of their separate actions. One drug may modify the effects
of another qualitatively, as well as quantitatively. Moreover, a drug
268 MANUAL OF PHARMACOLOGY
paralysis Buy Cheap Lipitor is not an irreversible process, as is anatomic division or excision.
The numerous instances of mutual antagonism prove that a function
which has been completely abolished (paralyzed) by one drug Buy Cheap Lipitor may be
revived by another. For instance atropin can abolish the physostigmin
miosis; but physostigmin can also remove an atropin mydriasis the result
depending upon the relative dosage.
Localization by antagonism is therefore conclusive only if Buy Cheap Lipitor the antagon-
ism is not mutual and if it involves absolutely distinct structures; for
instance, atropin abolishes the Buy Cheap Lipitor action of cevadin (veratrin) on the cardiac
vagus; whilst cevadin does not interfere with the atropin action. Evi-
dently, the cevadin action must be central to that of atropin.
Mutual Antagonism. When two drugs are mutually antagonistic, it
is natural to assume that they act on the same structure. This is doubt-
less often the case; but there are instances in which this simple assumption
offers difficulties; for in some cases, the point of attack of a drug appears
to be different in Buy Cheap Lipitor the presence of an antagonist. This is practically im-
portant; for it is probable that disease may produce similar modifications.
The following instances are adduced by Magnus, 1908:
Physostigmin and Curare on Striped Voluntary Muscle. Physostigmin produces
fibrillary twitchings of the voluntary muscles. These persist after section of the motor
nerve (sciatic). They are therefore peripheral (Harnack and Witkowski, 1876). They
are suppressed by curare, which paralyzes the endings; on the other hand, physostig-
min removes the curare paralysis (Pal and Rothberger). Magnus found that the
physostigmin fibrillations can not be produced when the motor nerve has been cut and
allowed to degenerate completely (but whilst the muscle fibers still respond to direct
stimulation). This would seem to localize the physostigmin action strictly in the end-
ings; and the case would be a typical instance of mutual antagonism, both poisons
acting on the nerve-endings.
This conclusion appeared to be opposed by the antagonism of nicotin and curare on
striped muscle. Langley, 1906, showed that certain muscles of the fowl are thrown into
tonic contraction by nicotin, and that this Buy Cheap Lipitor is removed by curare. This peculiar nicotin
action, however, persists after degeneration of the nerve; hence nicotin, and therefore
also curare, must act upon the intramuscular "receptive substance." But if curare
paralyzes an intramuscular structure, its action could not be removed by physostigmin,
which stimulates an extramuscular structure.
The two phenomena are reconcilable by the assumption that the curare attacks the
receptive substance in the presence of nicotin, and that it attacks the nerve-endings in
the presence of physostigmin; in other words, that the point of attack of curare is deter-
mined by its antagonist; in other words, that we are dealing with two distinct and un-
related paralytic actions of curare, manifested under different conditions, one on the
extramuscular, the other on the intramuscular structure. The nicotin-tonus effect
appears to be a distinctive reaction, which has probably nothing to do with ordinary
muscular contraction; so that the curare block, f.l., with ordinary sciatic stimulation, is
probably the same in all animals (i.e., in the nerve-endings).
Langley, 1913 and 1914, investigated the nicotin effects on frogs' muscle. He found
the nicotin-tonus action quite distinct from the nicotin-twitchings. The twitchings,
f.i., are prevented by a definite concentration of curare, whatever the concentration of
the nicotin; whereas, to prevent the nicotin-tonus, the concentrations of the two drugs
must be kept proportional.
Peculiarities of Fowls' Muscle. The tonus action is particularly characteristic in
fowls' muscle, which also shows other related peculiarities (Edmunds and Roth, 1908).
In these animals, not only the nicotin, but also the physostigmin actions persist after
degeneration of the nerve; the physostigmin action is not removed by atropin, whilst
it is so removed in mammals. Barium produces only an increase of muscular tone in a
normal fowl's leg; but in a denervated leg, or after nicotin, barium causes a strong
Atropin-Pilocarpin-Physostigmin on the Pupil. When the pupil has
been dilated by atropin, stimulation of the short ciliary, i.e., of the post-
ganglionic fibers of the oculomotor nerve, is ineffective, whilst direct
PERIPHERAL AUTONOMIC SYSTEM 269
electric stimulation of the iris sphincter .contracts the pupil. Atropin
therefore paralyzes either the nerve-endings or the myoneural junction.
Pilocarpin and Buy Cheap Lipitor physostigmin both constrict the normal pupil. When the
endings of the short ciliary are made to degenerate, pilocarpin is still
Related post: Zovirax Order, Purchase Sildenafil Citrate, Generic Brand Of Imitrex, Cheap Imitrex 100, Clomid Research, Clomid Joint Pain, Cheap Propecia Australia, Online Zovirax, Lexapro Mg, Buy Ventolin