Cyclosomatostatin-induced catalepsy in the aged rat: a response to levodopa, diphenhydramine and nicotine

Abstract

A decrease in somatostatin level is observed in parkinsonian brain. We recently reported that rats given an intracerebroventricular injection of a somatostatin antagonist, cyclosomatostatin, fall into catalepsy; the effect was observed in aged but not young animals. To evaluate the predictive validity of the cyclosomatostatin-induced catalepsy as a model of extrapyramidal disorders, the sensitivity of this catalepsy to clinically effective antiparkinsonian agents was determined. We examined the effects of levodopa and histamine antagonists; also, given an inverse association between Parkinson's disease and tobacco smoking, nicotine was tested. The experiments were conducted using 27-28month-old male Wistar rats. Catalepsy was measured using the bar test. Cyclosomatostatin-induced catalepsy was strongly antagonized by levodopa, which indicates a role for central dopaminergic deficiency in this model. Similarly, histamine H 1receptor antagonist, diphenhydramine, exhibited anticataleptic activity; in contrast, antagonists at H 2and H 3-receptors were without effect. Cataleptic response was inhibited by nicotine; the nicotine sensitivity distinguishes this catalepsy from other models, in particular, from haloperidol-induced catalepsy. Diphenhydramine and nicotine alone only partly suppressed catalepsy; however, coadministration of these drugs almost totally reversed the cataleptogenic effect of cyclosomatostatin. Thus, a similarity between the cyclosomatostatininduced catalepsy and Parkinson's disease with regard to the sensitivity to anti-parkinsonian agents was found. This supports the validity of the model as well as the role of somatostatinergic deficiency in the mechanism of parkinsonian symptoms. Coadministration of diphenhydramine and nicotine appears to be a promising treatment for extrapyramidal disorders in Parkinson's disease.

Sustainable Electrochemical Benzylic C−H Oxidation Using MeOH as an Oxygen Source

“…Diphenhydramine is a first‐generation antihistamine, which is mainly used in the treatment of allergies. It is also used in the management of drug‐induced parkinsonism [29] . Synthesis of cinnarizine ( 67 ) from 48 was accomplished in three steps [30] .…”

“…Propylbenzenes and electronically distinct ethylbenzenes were also excellent substrates . In particular, the reaction tolerated useful functionalities such as halides (14 and 16-21), carbonyl group (26 and 27), ester (28), boronic acid (29), carboxylic acid (30), sulfonyl group (31), sulfamide (32), [25] and nitro group (33). Acetophenone derivatives with strong electron-withdrawing groups at the para positions, which are challenging to prepare via the commonly used FriedelÀ Crafts acylation reactions, were obtained in moderate yields by our method.…”

“…It is also used in the management of drug-induced parkinsonism. [29] Synthesis of cinnarizine (67) from 48 was accomplished in three steps. [30] Flunarizine (70) was synthesized from ketone 50 via the same strategy.…”