Further studies on the hypoxia produced by canatoxin in rats

Canatoxin, a convulsant neurotoxin from the seeds of Canavalia ensiformis, induces lipoxygenase-dependent hypoxia in rats which is blocked by hexamethonium. The purpose of the present study was to examine the relationship between canatoxin-induced hypoxia and bronchoconstriction. Since several effects of the toxin are very similar to those described for morphine and opioid-like peptides, the effects of opioid antagonists were also investigated. Pretreatment of male, adult Wistar rats (200-250 g) with cyproheptadine (80 ug/kg, ip, N=6) and isoproterenol (100 ug/kg, ip, N+6) partially blocked (% variation of pO2:CNTX alone: -26.67 ñ 2.56, N=6; with cyproheptadine: 16.15 ñ 2.97*, N=6; with isoproterenol: 17.73 ñ 1.93*, N=6; *P<0.05 as compared to CNTX alone) the hypoxia but no effect was observed with diphenhydramine (2 mg/kg, ip, N=6) or atrophine (2 mg/kg, ip, N=6). The hypoxemic effect of canatoxin (100 ug/kg iv 20 min, N=6) was also almost completely blocked with either naloxone (1 mg/kg, sc, N=6) or naltrexone (5 mg/kg, sc, N=6). The results presented here provide evidence suggesting that both opioid peptides and bronchoconstriction seem to play a role in the hypoxia caused by canatoxin

Nitrous oxide antagonizes CNS stimulation by laudanosine in mice.

We have investigated whether nitrous oxide antagonizes or augments the CNS stimulant action of laudanosine in mice by comparing the mean convulsive doses (CD50 (SE] of a control group and those following pretreatment with 65% nitrous oxide in oxygen for 20 and 180 min. Nitrous oxide significantly increased CD50 from 46.8 (1.4) mg kg-1 of control to 57.3 (1.3) mg kg-1 at 20 min and 53.5 (1.7) mg kg-1 at 180 min. The attenuation of the effect of nitrous oxide at 180 min, suggestive of possible partial drug tolerance, was not statistically significant. These findings indicate that nitrous oxide antagonizes the CNS stimulating action of laudanosine.

Avaliaçäo clínica de um novo analgésico antagomista dos ópio: meptazinol / Clinical avaliation of a new analgesic opium antagonist: meptazinol

O efeito analgésico e, em especial, a segurança da administraçäo intramuscular de100 mg de meptazionol foram avaliados em estudo aberto, em 42 pacientes portadores de dor intensa ou muito intensa, resultante de causas diversas, tanto clinicas como pós-cirúrgicas. Os resultados indicaram que meptazinol é um analgésico eficaz, com poucos e toleráveis efeitos secundários, sendo a vertigem/tontura o mais freqüente, com incidência de 23,8%. O alívio da dor instalou-se em período inferior a 30 minutos, sendo máximo até 2 horas após a medicaçäo e perdurando pelo tempo de observaçäo clíncia, que foi de 6 horas, em grau entre acentuado e completo. Em relaçäo a sinais vitais e sedaçäo, näo existiu diferença clínica entre o período pré-administraçäo e os períodos de observaçäo, salientando-se portanto, a segurança do emprego do meptazimol

[Naloxone--a clinical study on dosage (author's transl)]. / Naloxon. (Eine klinische Untersuchung zur Frage der Dosierung).

In 50 Patients (group I) anaesthetized with neuroleptanalgesia and in 20 patients (group II) anaesthetized with moderate doses of fentanyl given to supplement nitrous oxide - halothane anaesthesia the postoperative respiratory depression was antagonized with naloxone. Each patient was carefully titrated with small increments of naloxone (40 microgram) given in 1-2 minute intervals. A reversal of the narcotic induced respiratory depression was taken for granted, when respiratory rate exceeded 12/min, tidal volume and blood gas analysis showed normal values. The results demonstrated a correlation between the need for naloxone and the time interval from the last administration of fentanyl to the completion of the operation and the fentanyl consumption per hour. When the interval was less than 1 hour more than 90% of the patients required postsurgical naloxone for respiratory inadequacy. The mean naloxone dose was 20 to 30% of the fentanyl dose given per hour: 1,2 microgram/kg naloxone reversed 4,9 microgram/kg.h fentanyl (group I) and 0,6 microgram/kg naloxone reversed 2,9 microgram/kg.h fentanyl (group II) respectively. To prevent renarcotization it is recommended to administer naloxone i.m. 30 to 45 min after the last naloxone-injection using the total i.v. dose.

Neuronal peptide (enkephalin) receptors in the ear artery of the rabbit.

Methionine-enkephalin methylester (MEM) and leucine-enkephalin (LE) inhabit the vasoconstrictor responses of the rabbit ear artery to nerve stimulation by acting on a specific neuronal peptide (enkephalin)-receptor insensitive to opiate agonists. The tetrapeptide: H-Tyr-Gly-Phe-Leu-OCH3 is ineffective. This is the first instance of enkephalins acting in an organ devoid of receptors. In a new test for the analysis of opiate receptors, MEM (ID50=6.9 X 10(-9) M) was a potent inhibitor of transmission. The presence was shown of opiate receptors in the brain which were insensitive to high i.v. or intraventricular doses of enkephalins. It is concluded that enkephalins are not natural ligands to the opiate receptors, but that some of the receptors confuse these structures because of similar characteristics which determine the binding of both opiates and peptides.

Recent developments in opiate research and their implications for psychiatry.

Considerable progress in opiate research has been made during the last few years regarding the identification and localization of opiate receptors in vitro and in vivo, the analysis of drug-receptor interactions and the characterization of an endogenous ligand of the opiate receptor. There is little evidence that effects induced by chronic exposure to opiates - development of tolerance and dependence -are due to changes in opiate receptor mechanisms; it is supposed that the adaptive changes occur mainly in the chain of events triggered by the drug-receptor interaction. Such changes may be directly or indirectly related to the metabolism of neurotransmitters and/or cyclic nucleotides. The obvious links between physical and psychic equivalents of opiate dependence are discussed. Present data points to the significance of brain stem and limbic structures in both these processes, monoamines probably playing an important role. Relations between psychic manifestations of opiate addiction and mental disorders are pointed out.