FENOTIAZYNY — the group of the chemical compounds which are derivatives of a fenotiazin many from to-rykh found broad application as pharmaceuticals.
Fenotiazin represents heterocyclic compound; C12H9NS:
Pale yellow Christal of l iches cue powder. We will dissolve in water and ether a little, we will easily dissolve in hot alcohol, gpl 182 °; pier. weight (weight) 199,26. A. Bernthsen is synthesized in 1883. It is applied in veterinary practice as insecticidal and a helminthicide.
As pharmaceuticals derivatives of a fenotiazin were offered in the middle of 20 century. The first F., implemented in medical practice, were antihistaminic drugs etizin and isopromethazine (see), and also a holino-blocker Dinezinum (see). Synthesis and studying pharmakol had special value. properties of Chlorpromazinum (see Aminazine), to-ry was an ancestor of a new class of medicinal substances — neuroleptics (see. To it role of n of t ich esky means).
The widest range pharmakol. activities possess alkyl -
aminoalkyl derivatives of a fenotiazin. They exert impact on c. N of page, causing calming, antiemetic and nek-ry other effects, possess an antigist mine, spasmolytic, adreno-and holinoblokiruyushchy action, exponentiate effect of anesthetics, hypnotic drugs and analgetic substances.
Absolute importance for manifestation of these or those pharmakol. properties at F. the structure of the side chain attached to a nitrogen atom in the 10th provision of a molecule of a fenotiazin and structure of a chain in the 2nd situation have. So, T., belonging to neuroleptics, in the 10th situation have a side chain of type — CH2 — CH2 — CH2-NR, i.e. the factor defining existence of antipsychotic properties is the intramolecular distance of a side chain equal to length of three methylene groups between nitrogen atoms in the 10th situation F. and side chain. Branching of a side chain usually leads to decrease in antipsychotic activity. Deputies in the 2nd provision of a molecule F. neuroleptics from among derivatives of a fenotiazin can have halogen or the following radicals: — CH3 — OSN? >— CF3 — S02N(CH3)2 — CN. Assume that such deputies shall have an electronic acceptor - nymi properties. Ilo to a structure of an alkyl side chain neuroleptics from among derivatives of a fenotiazin can be divided into three groups: aliphatic, piperidinovy and pi-perazinovy.
The most active neuroleptics among F. drugs of piperazinovy group, napr, Triphtazinum (see), etaperazin (see), ftorfenazin are (see), the optimum combination of elements of a side chain and the radical (usually groups — CF3) in the 2nd provision of a molecule F is characteristic of a chemical structure to-rykh. Assume that connections of such structure have conformational looking alike a molecule of dopamine. It gives them a high rnost of a complement in relation to the central dopamine receptors and ability it is easy to contact them. Meanwhile it is known that degree of antipsychotic activity is proportional to ability of substances to block dofaminergichesky transfer in nek-ry departments of a brain. Except neuroleptics among F. there are also other drugs influencing c. N of page, napr, antidepressant ftoratsizin (see), an antiemetic thiethylperazine, etc.
During the replacement of an alkyl side chain in the 10th situation on acylic (— WITH — CH2—CH2—NR, R1), i.e. during the receiving 10-atsilnroizvodny
FENTANYL of £25
a fenotiazin, significantly changes their range pharmakol. activities. At such F. almost completely the central neurotropic activity and nek-ry types of peripheral action disappears (e.g., adrenoceptor blocking, antihistaminic), but at the same time spasmolytic activity amplifies, anti-quinsy lny and an antio rhythmic properties appear.
To 10-acylderivative a fenotiazina with the expressed anti-anginal activity belong nonakhlazin (see) and Chloracizinum (see). They improve blood supply and the energy balance of a myocardium, possess spasmolytic action. In the mechanism of their action there is an adrenergic component. The fenotiazina belongs to 10-acylderivative also antiarrhytmic means an Ethmosinum (see). On a chemical structure and properties it is similar to nonakhlazi-number and Chloracizinum, but the antio possesses rhythmic action preferential. It is applied at an extra-sistoliyakh, attacks of ciliary, atrial arrhythmias, a Bouveret's disease, at the arrhythmias connected with overdose of cardiac glycosides.
Except the drugs noted above to F. belongs methylene blue (see), to-ry apply in medical practice of hl. obr. as an antiseptic agent and as an antidote at nek-ry poisonings.
Bibliography: The medicines used in psychiatry under the editorship of G. Ya. Avra tsky, page 18, M., 1980; Love
mo in B. I. and Rajevski K. S. Pharmakologicheskaya and the clinical characteristic нейролептиков-10-алкилпипера-зинилпропильных derivatives of a fenotiazin, in book: Usp. in creation of new pharmaceuticals, under the editorship of D. A. Har-kevich, page 33, M., 1973; R and e in -
with to and y To. C. Pharmacology of neuroleptics, page 32, M., 1976; Psychopharmacolo-gical agents, ed. by M. Gordon, v. 2, p. 2, N. Y — L, 1967. K. S. Rayevsky.