Hypothermia, drug-induced

Johannesen L, Vicente J, Mason JW et al (2016) Late sodium current block for drug-induced long QT syndrome results from a prospective clinical trial. CUn Pharmacol Ther 99 214—223 Kang IS, Fumiaki I, Pyun WB (2016) Therapeutic hypothermia for cardioprotection in acute myocardial infarction. Yonsei Med J 57 291-297... 

MAC values for a particular volatile anaesthetic are highest in neonates and lowest in the elderly although the explanation for this is not clear. MAC values are unaffected by gender, duration of exposure, and acid-base status. MAC is reduced by induced hypotension, hypothermia and hypoxia. Drugs... 

Marijuana has bear used as a traditional medicine and a pleasure-inducing drug for thousands of years. The mqor pharmacologically active constituent of marijuana is A -tetrahydrocannabinol (A -THC). The administration of A -THC to experimental animals and humans ehdts a variety of biological responses in various tissues and organs, particularly in the central nervous system. For example, A -THC induces reduced spontaneous motor activity, immobility, analgesia, impairment of short-term memory, and hypothermia in experimental animals and altered perception, euphoria, and hallucination in humans (Dewey, 1986). The mechanisms of these actions of A -THC ranained elusive until recently. 

Most frequently used in these antagonism tests are reserpine and the benzo-quinolizine derivatives, tetrabenazine and Ro-4-1284. The latter 2 drugs have a more rapid onset of action and a more selective activity on the central nervous systems (CNS) than reserpine. Antagonism by test compounds of the induced hypothermia, ptosis (eyelid closure), miosis (decreased pupil diameter), and sedation is measured either separately or combined. Evidence has been presented [8] that hypothermia antagonism is a better indicator of CNS activity, as ptosis and miosis can be influenced also by drugs with a peripheral action [9]. 

Diaryl derivatives with a hydroxyl group at another site in the alkylene chain are represented by BRL 14342 (78). Some structural relationship with (76) and (77) may be seen in this compound, which is currently undergoing tolerance and EEG studies in human volunteers. The results suggest that (78) is a potent nondepressant CNS-active drug [220]. The compound is a 60 40 mixture of the two possible diastereoisomers (racemates ), which are of approximately equal activity [220]. It is stated that the (-)-isomer shows fewer peripheral anticholinergic effects than the (+)-form. The (+)-isomer is more active than the (—)-isomer in the reserpine reversal test at low doses, but the 2 isomers have rou Iy equal effects in tests on prevention of reserpine-induced hypothermia [221]. Because (78) has 2 chiral centres it is not clear if the optically active compounds are single diastereoisomers or mixtures of 2 of them. 

---