BM-5, a centrally active partial muscarinic agonist with low tremorogenic activity. In vivo and in vitro studies.

Abstract

The acute and chronic effects of the centrally active oxotremorine analog, BM-5, [N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)-acetamide] were examined in rats and mice. In vivo studies in mice and rats indicated that this compound is a partial muscarinic agonist with large regional differences in its efficacy: BM-5 produced low tremor in doses which evoke full salivary response. The maximal tremor response to BM-5 was much smaller than that produced by oxotremorine, while the maximal salivary response to BM-5 was greater than that evoked by oxotremorine. The tremor response to BM-5 was bell-shaped, the peak dose being around 2 mg/kg. In contrast, the salivary response increased with increasing doses of BM-5. The apparent muscarinic antagonist properties of higher doses of BM-5 were specific to the striatum in which BM-5 (0.05-10 mg/kg) caused significant decreases in the level of acetylcholine while these levels were unaltered in the cerebral cortex, hippocampus, and brainstem. Pretreatment of rats with BM-5 (5 mg/kg) also prevented the increase in striatal acetylcholine induced by oxotremorine (0.75 mg/kg). Chronic treatment of mice with BM-5 (0.2-2 mg/kg) for 14 days also showed that BM-5 at higher doses, behaved as an antagonist, since it caused supersensitivity to oxotremorine on the tremor response. In addition, the number of receptor sites, as measured by binding of 3H-3-quinuclidinyl benzilate (3H-3-QNB), was increased in the striatum while no similar increase was observed in other brain areas.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: C Engström, A Undén, H Ladinsky, S Consolo, T Bartfai
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 91 Issue 2 Pg. 161-7 ( 1987) ISSN: 0033-3158 [Print] Germany
• PMID: 3107028 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Parasympathomimetics
• Pyrrolidines
• Oxotremorine
• N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide
• Choline
• Acetylcholine

Topics

• Acetylcholine (metabolism)
• Animals
• Body Temperature (drug effects)
• Brain (metabolism)
• Choline (metabolism)
• Dose-Response Relationship, Drug
• In Vitro Techniques
• Mice
• Oxotremorine (pharmacology)
• Parasympathomimetics (metabolism, pharmacology)
• Pyrrolidines (metabolism, pharmacology)
• Rats
• Salivation (drug effects)
• Tremor (chemically induced)