Tubocurarine-like drugs

Aceclidine is mostly used in ophthalmology for constriction of the pupil and reduction of intraocular pressure in glaucoma. Oxylidine is being used as a tranquilliser in patients with neurotic states and early states of hypertension. It is also recommended for the treatment of cerebral atherosclerosis. Its oral dose is 0.02—0.5 g. Qualidile is a curare-like drug used in general anaesthesia. The preparation is injected intravenously at a dose of 1 mg kg S muscle relaxation lasts for 10 minutes, slight inhibition of respiration being observed. A dose of 2 mg kg produces complete relaxation of the skeletal muscles, accompanied by apnoea. In spite of the fact that the review is well documented, it is difficult to form an idea about the clinical merits of these compounds. Some clinical information has been published recently a comparison of Qualidile with NiV -diallyl-bisnortoxiferine or tubocurarine chlorides loc. cit.) would be of special interest. 

Curare-like muscle relaxants act by blocking acetylcholine receptor sites, thus eliminating transmission of nerve impulses at the neuromuscular junction. There are two acetylcholine-like groupings in the molecules, and the drugs, therefore, probably span and block several receptor sites. The neurotransmitter acetylcholine is also a quaternary ammonium compound. The natural material present in curare is tubocurarine, a complex alkaloid that is a mono-quaternary salt. Under physiological conditions, the tertiary amine will be almost completely protonated (see Section 4.9), and the compound will similarly possess two positively charged centres. 

The discovery of several important drugs can be traced back to the medicinal or ritual use of specific plants in a non-Western culture. Alkaloids like quinine, emetine, physostigmine and tubocurarine were all discovered because their plant producer had been identified for a particular activity by a native culture.74 The World Health Organization (WHO) has estimated that 80% of the world s population rely mainly on plant-based traditional medicine for their primary health.75 There is, therefore, an enormous past and current literature on the human use of plants. 

Like D-tubocurarine, alcuronium does not undergo biotransformation. Excretion occurs mainly in the urine (80-85%), but, as with D-tubocurarine, some is also excreted in the bile (15-20%) (1). Persistent relaxation has been reported in renal insufficiency (2) and the drug is relatively contraindicated in this condition. 

Hypotension may occur with tubocurarine and with the spasmolytic drug tizanidine. In the case of tubocurarine, the decrease in blood pressure may be due partly to histamine release and also to ganglionic blockade. Tizanidine causes hypotension via alpha2 adrenoceptor activation like its congener clonidine. The answer is (D). 

Attempts to simplify tubocurarine were made while it was still thought to have two quarternized amino-groups, whereas it has in fact only one (Everett, Lowe and Wilkinson, 1970). In spite of this misconception, some very useful drugs were developed. It was related in Section 2.0 how Crum Brown and Fraser (1869) had shown that various alkaloids acquire curare-like properties by methylation to quaternary ammonium bases. Even simple aliphatic quaternary... 

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