methylatropine and Tremor

Behavioral responses to atropine in rats exposed to the potent anticholinesterase agents Soman and Sarin were studied. Atropine itself produced limb-shakes and certain stereotyped activities, in a dose-dependent manner. The neurotoxicity elicited by Soman and Sarin was antagonized by atropine, while at the same time the responses induced by the latter were attenuated. In contrast, where rats were challenged with atropine 6-72 h after giving single doses of Soman or Sarin, the limb-shake myoclonus was markedly enhanced. The atropine-induced stereotypies were not, however, significantly affected, except for an increase seen at 24 h after Sarin treatment. Repeated treatment with Soman for 3 wk also led to similar supersensitivity of atropine-induced responses. The peripheral muscarinic receptor antagonist, methylatropine, produced no such hyperactivity on its own or at any time after anticholinesterase exposure. The rapid occurrence of hypersensitivity to antimuscarinic compounds following exposure to these anticholinesterases, therefore, suggests the need for observation of subjects who are poisoned with such agents and treated with antimuscarinics, for adverse reactions such as myoclonus during the critically sensitive period, especially if repeated antimuscarinic therapy is carried out.

Topics: Animals; Atropine; Atropine Derivatives; Drug Hypersensitivity; Male; Organophosphorus Compounds; Parasympatholytics; Rats; Rats, Inbred Strains; Sarin; Soman; Stereotyped Behavior; Tremor

Acute and long-term (3 weeks) effects of thyrotropin releasing hormone (TRH) on behavior were investigated in mice. A single injection of TRH produced Straub tail, tremor and salivation, as well as stereotyped responses, such as head bobbing, jaw movement, digging and sniffing. Dose- and time-dependency for the effects of TRH were different depending on each response. A single injection of TRH at a low dose of 2.5 mg/kg SC did not produce stereotypy but this behavior was induced when this dose of TRH was administered in combination with atropine (3 mg/kg IP). In addition, a single low dose of TRH elicited tremor and salivation which were potentiated by physostigmine (0.1 mg/kg IP). A single high dose (20 mg/kg IP) produced marked tremor and salivation which were conversely blocked by atropine. Following daily administration of TRH at a low dose of 2.5 mg/kg SC for 21 days, stereotyped behavior was progressively increased whereas tremor and salivation were decreased. This increase in stereotyped behavior was inhibited by haloperidol (1 mg/kg IP) or physostigmine (0.1 mg/kg IP). When saline was administered instead of TRH for 3 days after long-term administration of TRH, sterotyped behavior was maintained for 2 days but thereafter decreased to some extent. When TRH (1.25 mg/kg SC) was again administered at this stage, there was a marked increase in sterotyped response. These results suggest that TRH induces dopaminergic activation, accompanied by both cholinergic inhibition and cholinergic activation, and that the former is potentiated while the latter is reduced after daily administration of TRH.

Topics: Animals; Atropine; Atropine Derivatives; Behavior, Animal; Dose-Response Relationship, Drug; Haloperidol; Humans; Male; Mice; Parasympathetic Nervous System; Physostigmine; Receptors, Dopamine; Salivation; Stereotyped Behavior; Thyrotropin-Releasing Hormone; Time Factors; Tremor