PROZERIN (joint venture. And) — antikholinesterazny means of preferential peripheral action. N-(meta-Dimetilkarbamoiloksifenil) - trimetil-ammonium methyl sulfate; With 12 N 20 N 2 O 3 • CH 3 SO 4 :
Inodorous white crystal powder, bitter taste. It is hygroscopic. On light gets a pink shade. Let's very easily dissolve in water (1: 10), it is easy — in alcohol (1: 5). Water solutions (pH 5,9 — 7,5) will sterilize at t ° 100 ° within 30 min. Pier. weight (weight) 334,39; t°pl 142 — 146 °.
The item is the simplified synthetic analog of physostigmine and concerns to group of carbamates (see. Carbamic connections ), contains the karbamoiloksifenilny group providing molecular interaction of drug with cholinesterase. On pharmakol. to properties it is close to to physostigmine (see) and to Galantaminum (see). However unlike these drugs in therapeutic doses practically does not affect c. the N of page since is quaternary ammonium compound and therefore badly gets through a blood-brain barrier.
Along with braking of activity of cholinesterase P. can cause the effects which are not connected with its antikholinesterazny properties (the postsynaptic sensibilizing and presynaptic facilitating action) which, apparently, are shown preferential by action on neuromuscular transmission.
After introduction in therapeutic doses of P. is defined in blood during 3 — 5 hours that approximately corresponds to duration of braking of cholinesterase. In went. - kish. P.'s path it is soaked up not completely. It is removed by kidneys partially in not changed look, partially in the form of metabolites.
Items use hl. obr. as the antagonist of kurarepodobny substances (see) not depolarizing like action. At the same time in comparison with Galantaminum its action is shown slightly quicker, but is less long in this connection P. sometimes apply in combination with Galantaminum. Besides, P. use for treatment of paresis and paralyzes of the central origin, in particular in the recovery period of poliomyelitis, and also for diagnosis and treatment of a myasthenia. However it must be kept in mind that P.'s use for diagnosis of a myasthenia is unsafe since at rather small overdose of drug there can be a depolyarizatsionny neuromuscular block.
The item is a strong stimulator of smooth muscles of internals and therefore it is used for the prevention and treatment of an atony of intestines and a bladder. Earlier it was recommended also for stimulation of patrimonial activity. However has no broad use in modern obstetric practice in connection with introduction of more effective methods of treatment of weakness of patrimonial activity.
In ophthalmologic practice of P. apply as a miotoc though its action is less long in comparison with Arminum and other irreversible inhibitors of cholinesterase.
The item is appointed usually subcutaneously and inside. Under skin the adult enter on 0,5 — 1 ml 0,05% of solution of 1 — 2 time a day. To children appoint on 0,1 ml 0,05% of solution to 1 year of life, but no more than 0,75 ml on one injection. Inside the adult appoint 0,01 — 0,015 g 2 — 3 times a day; to children up to 10 years on 0,001 g for 1 year of life a day, to children 10 years not above the general daily dose of 0,01 g are more senior.
At P.'s use as antagonist of kurarepodobny substances of not depolarizing type of action after preliminary atropinization enter 3 ml of 0,05% of solution P into a vein. Within only 20 — 30 min. it is possible to enter 10 — 12 ml of 0,05% of solution.
For treatment of a myasthenia of P. it is possible to appoint along with atropine for the purpose of stopping of undesirable m - cholinomimetic effects (bradycardia, hypersalivation, etc.). For stopping of myasthenic crisis of P. enter intravenously on 0,5 — 1 ml 0,05% of solution then pass to subcutaneous injections of drug. The highest doses for adults: inside one-time 0,015 g, daily 0,05 g; under skin of one-time 0,002 g, daily 0,006 g.
Side effect and symptoms of intoxication of P. are shown by a miosis, hypersalivation, nausea, strengthening of a vermicular movement of intestines, a diarrhea, a frequent urination, muscular fibrillations, the general weakness to which stopping it is possible to apply atropine, Methacinum or other holinoblokiruyushchy drugs which are fiziol. antagonists of the Item. Apply reaktivator of cholinesterase to stopping of the neuromuscular block called by P. (e.g., dipiroksy).
Forms of release: powder, tablets on 0,015 g and ampoules on 1 ml of 0,05% of solution. Storage: in well corked banks from orange glass or in the soldered ampoules in the place protected from light.
Bibliography: Brooms S. N. and Rozengart V. I. Cholinesterases and An-tikholinesteraznye of substance, L., 1964; Prozorovsky V. B. and Savateev N. V. Neantikholinesteraznye mechanisms of action of antikholinesterazny means, L., 1976.
S. N. Golikov.