Hypotensive and bradycardic effects of talipexole (B-HT 920) in anaesthetized rabbits are antagonized by metoclopramide but not by yohimbine.

The interactions of talipexole (B-HT 920) and clonidine with selective alpha-adrenoceptor antagonists, yohimbine (alpha 2) and prazosin (alpha 1), as well as with dopamine receptor antagonists, metoclopramide (D2), domperidone (D2) and SCH23,390 (D1) were investigated in anaesthetized rabbits after i.v. administration.

Physical dependence capacity of brotizolam in rhesus monkeys. 2nd communication: primary dependence and barbital substitution.

The degree of physical dependence induced by oral administration of brotizolam (2-bromo-4-(2-chlorophenyl)-9-methyl-6H-thieno [3,2-f]-1,2,4-triazolo[4,3-a]-1,4-diazepine, We 941, Lendormin), triazolam, diazepam and nitrazepam in rhesus monkeys was evaluated in primary dependence studies. Substitution tests were performed in barbital-dependent animals. In the primary dependence studies, two dosages of each compound were administered for four weeks to compare the effects on motocoordination and development of body weight as well as the withdrawal symptoms after interruption of these chronic administrations.

Physical dependence capacity of brotizolam in rhesus monkeys. 1st communication: primary dependence studies.

Abstinence symptoms of doses acutely equi-effective on motocoordination of brotizolam (2-bromo-4-(2-chlorophenyl)-9-methyl-6H-thieno [3,2-f]-1,2,4-triazolo[4,3-a]-1,4-diazepine, We 941, Lendormin) and diazepam in rhesus monkeys were evaluated in a primary dependence study of 61 days. After termination of oral treatment with 3 X 5.4 mg/kg/d brotizolam and 3 X 13.

Differentiation of mu- and kappa-receptors by means of correlation of analgesic potency in vivo and receptor binding affinity in vitro of various opioid agonists.

For various opioid agonists (n = 35) an unsatisfactory correlation between analgesic activity in vivo (mouse) and receptor binding affinity (rat brain) in vitro was obtained. Excellent correlations were observed, however, after separation of the opioid agonists into two groups with mu- and kappa-receptor selectivity, respectively. The correlation of the analgesic potency with the affinity to the opioid kappa-receptor was very high for the group of kappa-agonists, while it was low for the group of mu-agonists.

Mr 2033 CL--a novel non-morphine-like opioid analgesic.

Mr 2033 CL is a very potent non-morphine-like opioid analgesic as shown in different test models and animal species. On a weight for weight basis, it is about 20 times more potent than morphine. The analgesic effects of Mr 2033 CL are supposed to be different from those of morphine and bremazocine because of individual sensitivity against selective antagonists like naloxone and Mr 2266 CL.

Pharmacology and hypnogenic properties of brotizolam in animals.

Brotizolam differs in pharmacological profile from other diazepines by virtue of its hypnogenic potency. It increases, whereas other diazepines reduce, sleep in the cat. With increasing doses, the latency to rapid eye movement sleep is lengthened and the proportion is reduced.

Diastereoisomeric N-tetrahydrofurfurylnoroxymorphones with opioid agonist--antagonist properties.

The two diastereoisomeric N-tetrahydrofurfurylnoroxymorphones and their hydrochlorides 1a and 1b have been prepared and studied pharmacologically; The N-(R)-tetrahydrofurfuryl derivative 1a proved to be an opioid agonist--antagonist and the N-(S)-tetrahydrofurfuryl derivative 1b a pure antagonist. As an analgesic, 1a is 25 times more potent than morphine, but it does not show morphine-like side effects in mice. In withdrawn morphine-dependent rhesus monkeys, 1a only partially suppresses abstinence.

[Pharmacologically active polymers. 9th communication: retard forms of morphine antagonists (author's transl)].

Acryloyl, methacryloyl, N-vinylcarbamoyl, and methacryloyl-glycyl derivatives of the morphine antagonist (--)-alpha-5,9-dimethyl-2-(3-furylmethyl)-2'-hydroxy-6,7-benzomorphane have been synthesized. The different unsaturated derivatives were copolymerized with appropriate comonomers to yield water-soluble polymers. Pharmacological tests in mice showed a 2--30 fold increase in duration of action in comparison to the free antagonist.

[Study on novel morphine antagonists in the animal experiment (author's transl)].

The morphine-antagonistic properties of 5 novel compounds, (--)N-(3-Furylmethyl)-nordesomorphine-hydrochloride-monohydrate (Wa 494-Cl), (--)N-(3-Furylmethyl)-3-hydroxy-morphinan-methansulfonate (Mr 1257 MS), (--)2-(3-Furylmethyl)-2'-hydroxy-5,9alpha-dimethyl-6,7-benzomorphan-methansulfonate (Mr 1452 MS), (+/-)-2-(3-Furylmethyl)-2'-hydroxy-5,9alpha-diethyl-6,7-benzomorphan-hydrochloride (Mr 1302 MS), (--)-N-(3-Furylmethyl)-noroxymorphon-methanesulfonate (Mr 1767 MS), have been examined with different methods on mice and cats. Their properties have been compared with those of naloxone, cyclazocine and nalorphine. The new test compounds showed a profile of action like naloxone.

[General pharmacology and secretion inhibitory action of (8r)-3alpha-hydroxy-8-isopropyl-1alphaH,5alphaH-tropanium bromide-(+/-)-tropate (ipratropiumbromide) (author's transl)].

(8r)-3alpha-Hydroxy-8-isopropyl-1alphaH,5alphaH-tropaniumbromide-(+/-)-tropate (ipratropiumbromide, Sch 1000) is a quaternary tropic acid tropane ester with pronounced anticholinergic activities (inhibition of secretion and spasmolysis). The effect of the substance of all parasympathetically innervated organs ist 1.4 to 2 times stronger than that of atropine.

Stereoisomeric 5,9-dimethyl-2'-hydroxy-2-tetrahydrofurfuryl-6,7-benzomorphans, strong analgesics with non-morphine-like action profiles.

The eight optically active stereoisomers and the corresponding four racemic forms of 5,9-dimethyl-2'-hydroxy-2-tetrahydrofurfuryl-6,7-benzomorphan (1) have been prepared. Depending on their configurations these compounds are potent analgesics or inactive substances in mice. The analgesics attain potencies up to about a hundred times that of morphine but they do not show morphine-like side effects in mice nor do they suppress abstinence in withdrawn morphine dependent monkeys.