Discriminative stimulus properties of phenytoin in the pigeon: determination via a cumulative dosing procedure

Pigeons were trained in a cumulative dosing procedure to emit one response in the presence of 15 mg/kg phenytoin and another response in the absence of phenytoin. After reliable discrimination was established, generalization tests with other anticonvulsant drugs were conducted. Ethosuximide (20-120 mg/kg) and methsuximide (25-100 mg/kg) engendered very little phenytoin-appropriate responding. Clonazepam (0.125-1 mg/kg) engendered more phenytoin-appropriate responding, but less than the training dose of phenytoin. Similar results were obtained when these drugs were administered in conventional single dose per session generalization tests. When tested in that fashion, mephenytoin (80 and 160 mg/kg) engendered some phenytoin-appropriate responding, but less than the training dose of phenytoin. Administering 10 mg/kg pentylenetetrazol in combination with 5, 10, 15, and 20 mg/kg cumulative doses of phenytoin reduced phenytoin-appropriate responding relative to levels obtained with these doses of phenytoin alone.     

Computer-aided spectrophotometric determination of multicomponent drugs

The conditions of least squares deconvolution by linear combination have been investigated in three-component systems. The significant effects of the main factors, the lack of significant interactions and the linear relationship of absorbance with the concentration of each component were established by using a 2³ factorial experiment design and by evaluating the results with a three-way analysis of variance. The content of active ingredients of three-component injections was determined by means of computer-aided evaluation of UV-spectra in systems that fulfilled these conditions.     

Reinforcing stimulus properties of drugs

The reinforcing efficacy of psychoactive drugs can reliably be studied in experimental animals by using procedures for drug self-administration. This property of drugs is used to predict qualitatively and quantitatively their abuse potential in humans. External factors like the dose of the drug, the schedule of drug availability and stimulus control are critically important in initiation, maintenance and cessation of self-administering behaviour. Drug-induced changes in the organism, including tolerance and physical dependence, may contribute more or less to the behaviour associated with drug use and consequently change the pattern of drug intake. Concerning the internal factors involved in the process by which a given drug consequence gains control over behaviour, it is suggested that addictive drugs may mimic the action of endogenous substances which are implicated in the physiological mechanisms underlying reinforcement. Neuropeptides e.g. those related to vasopressin, which are involved in the adaptation of the individual to his environment, may modulate the consequences of drug self-administration by interfering with the complex interaction of addictive drugs with brain homeostatic mechanisms. It is postulated that derangements in neuropeptide systems may be critical factors in the development of addictive behaviour.     

Water determination in drugs containing thiols

A new rapid analytical method is applied for water determination in -Mono-thioglycerol and Captopril tablets containing thiols, and therefore, not amenable for direct Karl Fischer titration. The method is based on the consecutive titration first of thiol by a novel reagent, and then of water by a conventional K. Fischer reagent in the same sample and cell with the electrometric ‘dead-stop’ location of the end point in both titrations. The new reagent consists of iodine, potassium iodide and sodium acetate in non-aqueous medium. Estimated repeatability and accuracy of both water and thiol determinations are satisfactory.     

Ganglion-blocking properties of atropine-like drugs

The ganglion-blocking properties of atropine, atropine methyl nitrate, oxyphenonium, poldine, methantheline and propantheline have been examined and compared with those of hexamethonium, mecamylamine, pentolinium and tetraethylammonium. The ganglion-blocking activity was assessed by stimulating the preganglionic nerve to the superior cervical ganglion and recording directly the percentage depression in the postganglionic action potentials. In this way any ambiguity due to the peripheral actions of the drugs was removed. As a group the atropine-like compounds are not markedly less potent than the ganglion-blocking agents, but their action is relatively transient. This work suggests that the ganglion-blocking action of atropine-like substances plays no part in their therapeutic effects.     

Aversive stimulus properties of drugs

A large number of psychoactive drugs have been considered to possess aversive stimulus properties, as demonstrated by their ability to induce conditioned taste aversion (CTA) in animals. However, the interpretation of the CTA effect is at present unclear. The hypothesis that drug-induced CTA is due to drug-induced conditioned “illness” is supported by the results of studies which implicate central emetic systems or their functional equivalents in the acquisition and recall of CTA induced by toxins. However, other data, obtained with agents which are not generally considered to be toxins, are not at present easily reconciled with this hypothesis. Conditioned taste aversion induced by self-administered drugs has been described as “paradoxical” in that some drugs will induce CTA at the same doses that maintain self-administration. A number of possible explanations for this apparent paradox are discussed, the majority of which are considered to be inadequate. The idea that the paradox of CTA induced by self-administered drugs is more apparent than real merits consideration. Possible relationships between studies of drug-induced CTA and operant studies of drugs as aversive agents are discussed. The most fruitful future avenues for research into the actions of drugs in the CTA procedure will probably be those that concentrate on providing answers to very basic questions such as whether or not drug-induced CTA is due to conditioned “illness”, and whether or not the phenomenon termed conditioned taste aversion actually involves conditioning with a drug-induced aversive stimulus.     

Electrochemical determination of oxytetracycline in veterinary drugs

Conductometric, potentiometric and cyclic voltammetric (CV) titration methods are proposed for determination of oxytetracycline (OTC), commonly used in veterinary. The electrochemical titration of OTC hydrochloride with NH(4)Mo(7)O(24), NaVO(3), NaOH, AgNO(3) and FeCl(3) as titrants are reported. The proposed methods were found to be highly precise, having a relative standard deviation (R.S.D.) below 1.0%. Proposed electrochemical titrations were successfully applied to the assay of commercial preparations: Tetrox, Tetramutin OT and Neox, containing the above-mentioned antibiotics. The validity of the methods was tested by the recovery studies of standard addition to pharmaceuticals and results were found to be satisfactory.     

抗结核药物含量测定方法研究进展

结核病是全世界由单一致病菌导致死亡最高的疾病,严重危害人类健康,因此保证抗结核类药物的质量具有重要意义。本文以常用抗结核药物为例,从国内外药典及文献报道两方面介绍了其含量测定方法,重点介绍高效液相色谱法,为建立快速、准确的高效液相色谱快速检验方法奠定基础。