Modification of drug-induced catatonia and tremors by quapazine in rats and mice.

Administration of perphenazine, tremorine, nicotine and harmine induced Parkinson-like symptoms in rats and mice. The efficacy of quipazine, a serotonin agonist, in antagonizing these drug-induced Parkinsonian symptoms was assessed. Combinations of this drug with other antiparkinsonian agents such as scopolamine, diphenhydramine and amantadine were also studied in the manifestation of Parkinson-like symptoms in the animal models. The results indicate that quipazine, a central serotonergic agent, counteracted some of the drug-induced symptoms of pseudoparkinsonism in laboratory animals. Cholinergic, dopaminergic and histaminergic receptors play an important role in the manifestations of these symptoms.

Synthesis and preliminary pharmacological activity of aminoalkoxy isosteres of glycolate ester anticholinergics.

A sides of 2-(N-substituted amino)alkoxy-1,1-diphenylethanols was synthesized and evaluated for anticholinergic activity. The compounds differ structurally from the glycolate ester-type anticholinergic compounds by the bioisosteric substitution of a methylene group for the ester carbonyl moiety. The ethers which result from this change have increased lipophilicity compared to their ability to inhibit perphenazine-induced catatonia in rats. Structure-activity relationships of the compounds are discussed.

Some initial animal and human pharmacological studies with benapryzine (BRL 1288).

1. The pA2 anti-acetylcholine activity in vitro for benapryzine was 6.55 compared with 9.02 for benzhexol.2. In vivo, the anti-acetylcholine activity of benapryzine relative to benzhexol was 0.038 as assessed by the mydriatic response of mice after subcutaneous administration. The relative activity assessed by the inhibition of pilocarpine-induced salivation was 0.13 after oral administration and 0.056 following subcutaneous administration of the drugs.3. Benapryzine had the same order of activity as benzhexol in inhibiting oxotremorine-induced tremors in mice.4. Benapryzine had anticonvulsant properties but no analgesic activity, whilst in high doses it antagonized the extrapyramidal symptoms induced by perphenazine in rats.5. In patients benapryzine was effective in reducing the symptoms of Parkinson's disease without overt anti-cholinergic effects or central hallucinogenic actions.6. Benapryzine abolished the excess tremor and reduced the rigidity and akinesia induced by physostigmine in Parkinsonian subjects.