Tranquillizing activity

Phiorog1iicino1-3,5-dimethyl-1-(2-amino-3-hydroxyhutyryl)ether is characterized by antiarrhythmic activity (176). 2,4-Diacylphloroglucinols were patented as compounds with pronounced anthelmintic activity (177). Phloroglucinol mono- and di-(2-chloroethyl) ethers have antispasmodic or tranquilizing activities (178). 2-(3,5-DiaLkoxyphenoxy)ethylamines have antispasmodic, choloretic, sedative, and vasodilating effects (179). 

Cyclization of the side chain onto the nitrogen atom leads to compounds with sedative and tranquilizing activity. The lack of structural specificity, that is, the fact that both positional isomers (41,43) show the same activity, is notable. Thus, condensation of the Grignard reagent from 2-bromopyridine with ben-zophenone affords the tertiary carbinol, 40. Catalytic reduction... 

Further chemical modification of the phenylpiperidine moiety has proven unusually fruitful in producing medicinal agents that affect the central nervous system. First, a series of compounds loosely related to the reversed meperidines produced several drugs with important antipsychotic activity. Further discussion of this pharmacologic activity, often referred to as major tranquilizer activity, will be found in the section on phenothiazines. The group led by Janssen took advantage of the chemistry of the... 

Substitution of an additional nitrogen atom onto the three-carbon side chain also serves to suppress tranquilizing activity at the expense of antispasmodic activity. Reaction of phenothia zine with epichlorohydrin by means of sodium hydride gives the epoxide 121. It should be noted that, even if initial attack in this reaction is on the epoxide, the alkoxide ion that would result from this nucleophilic addition can readily displace the adjacent chlorine to give the observed product. Opening of the oxirane with dimethylamine proceeds at the terminal position to afford the amino alcohol, 122. The amino alcohol is then converted to the halide (123). A displacement reaction with dimethylamine gives aminopromazine (124). ... 

CNS activity apparently is retained when the heterocycle is changed to an imidazolidinone. Alkylation of the anion from the imidazolidinone 138 with dimethylaminoethyl chloride affords imidoline (139), a compound with tranquilizer activity. 

The presence of a rather more complex substituent on the remote piperazine nitrogen atom is consistent with tranquilizing activity. The preparation of one such agent, 16, begins with reaction of thioxanthone 11 (obtained by a sequence analogous to that used to... 

Hypnotic and tranquilizing activity have pyrazolo [ 1,5-c] pyrimidines (71GEP2131790). 

To study the tranquilizing activity of l-(3, 3, 3 -trifluoropropyl)-3,7,10-trimethyl-silatrane its ability to potentiate the action of soporific agents, the influence on the spontaneous bioelectric activity of subcrustal formations of the brain, the protective effect against stress and the change in adrenalin and noradrenalin excretion in urine has been examined83. ... 

Pharmacological evaluation of the ethers and their water-soluble salts revealed a marked sedative action in dogs without any demonstrable antihypertensive effect. The tranquilizing activity differs from that of reserpine in that its onset occurs within minutes rather than hours and the duration of action is considerably shorter than that of reserpine. Cumulation is not evident on repeated administration there is no effect on the gastrointestinal tract and no diarrhea occurs (182). Clinically, the normal, as well as the 18-epi, ethers were found to be effective when given to patients with mild or moderate anxiety. However, the tranquilizing activity of the normal ethers is considerably higher, and for all practical purposes the 18-epi ethers are not suitable for human therapy. 

Miller and Weinberg (217) have published data on reserpine-like activity of simple trimethoxybenzoates of amino alcohols and have claimed tranquilizing activity for compounds like the following ... 

Pharmacological tests have shown that the substituent in position 2 produces an exaltation of the pharmacodynamic activity. These compounds have been claimed to be nervous system depressants, in particular with sedative, antiepileptic, and tranquilizing activity.100-105 Spasmolytic activity was shown by phenoxazine-10-carboxylic106 or phenoxazine-10-dithiocarboxylicalkylamino esters,78... 

There was continuing interest in the effects of 3-arylquinazolin-4-ones on the central nervous system (CNS) which resulted from the known activity of methaqualone (117 Ar = o-tolyl R = Me R = H). A most extensive literature is available on the metabolism, pharmacology, and analytical chemistry of methaqualone. The effects of varying the group R on CNS-depressant activity were reported. The structure 117 was associated with CNS-depressant and tranquilizing activities, and 3-o)-aminoalkyl-... 

In the phenothiazine area, it has been amply demonstrated that structural changes, in addition to producing expected quantitative changes in tranquilizing activity, also produce unexpected qualitative changes in biological activity. As a result antipruritic, antispasmodic, anticonvulsant, antibacterial, antiemetic, antimotion sickness, anthelmintic, and antidepressant compounds have been developed by molecular modification of the phenothiazines. 

Phenothiazines vary in degree of tranquilizing activity, but possess other useful biological properties. For purposes of this discussion, the index of... 

A phenothiazine with an aminoalkoxyalkyl carbamate side chain (XXI) has antitussive activity (dimethoxanate), but it is devoid of tranquilizing and conditioned escape response-blocking activity. Compound XXII similarly has antitussive activity, but is not stated to have analgetic and tranquilizing activities (14). 

Replacement of the sulfur atom in promazine by two methylene groups leads to imipramine (XXVI) which is not a tranquilizer, but is instead a clinically useful antidepressant agent (22, 25). Similarly, the dibenzocyclohepta-diene analog, amitriptylene (XXVII) (2), is devoid of tranquilizing activity and is a useful antidepressant like imipramine. 

Cyproheptadine (XXVIII) (36), an analog of amitriptylene, is devoid of antidepressant and tranquilizing activities, but possesses potent antiserotonin and antihistaminic activities. 

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