piperidines and 1-(3-cyclohexen-1-ylcarbonyl)-2-methylpiperidine

Two proprietary controlled-release (CR) formulations (CR55 and CR56) of 20% AI337220 (1-[3-cyclohexen-1-ylcarbonyl]-2-methylpiperidine) in an aqueous dispersion, and the same repellent formulated in water (W220), were compared with a repellent-free control for oviposition deterrent and larvicidal activity against natural populations of Stegomyia albopicta. A single application of each formulation (final concentration: 0.1%) prevented oviposition by St. albopicta for 4 wk, with highest deterrence (46%) observed for CR55 at 8 wk posttreatment. At the same application rate, each repellent formulation reduced larval activity in experimental containers by 100% through week 4 posttreatment and, for CR55, by 92-100% through week 8. In a municipal cemetery (Gainesville, Florida, USA), 1 application of CR55 or CR56 (final concentration: 0.1%) in concrete flower vases eliminated St. albopicta larvae for 10 wk. With formulation improvements to enhance efficacy at low repellent concentrations, AI3-37220 may have potential for use in the control of container-inhabiting mosquitoes.

Topics: Animals; Culicidae; Female; Insect Repellents; Insecticides; Larva; Mosquito Control; Oviposition; Piperidines

Both 1-methylisopropyl 2-(2-hydroxyethyl)piperidine-1-carboxylate, (Picaridin((R))) and cyclohex-3-enyl 2-methylpiperidin-1-yl ketone (AI3-37220; 220) have two asymmetric centers, and the four diastereoisomers of each compound are known to have differing degrees of mosquito-repellent activity according to quantitative behavioral assays conducted at the United States Department of Agriculture. Computational chemistry was used to identify the structural and configurational basis for repellent activity. Molecular overlay of the optimized geometries of the lowest energy conformers of the diastereoisomers was investigated to elucidate the role of chiral centers in 220 and Picaridin. It was found that the presence of a chiral carbon alpha to the nitrogen with the S configuration in the piperidine ring is essential to the three-dimensional arrangement of the atoms of the pharmacophore for effective repellent activity.

Topics: Animals; Biological Assay; Culicidae; DEET; Insect Repellents; Piperidines; Stereoisomerism; Structure-Activity Relationship

The repellents N,N-diethyl-3-methylbenzamide (deet) and racemic 2-methylpiperidinyl-3-cyclohexene-1-carboxamide (AI3-37220) were evaluated using two different laboratory bioassays to determine their relative effectiveness against host-seeking nymphs of the blacklegged tick, Ixodes scapularis Say, and the lone star tick, Amblyomma americanum (L.). In a petri dish bioassay, ticks were released within a ring of repellent on a horizontal filter paper disk. In the second bioassay, ticks were allowed to climb a vertical strip of filter paper whose central portion was treated with a repellent. Deet and AI3-37220 were more effective against I. scapularis than A. americanum nymphs. In the petri dish bioassay, none of the concentrations of deet or AI3-37220 tested confined A. americanum within the treated ring. However, in the vertical bioassay, both species exhibited avoidance of the repellents, and I. scapularis was repelled by much lower concentrations than A. americanum. I. scapularis were repelled by lower concentrations in the vertical bioassay than in the petri dish bioassay. Deet was slightly more effective against I. scapularis than AI3-37220 in both bioassays, but AI3-37220 was significantly more effective than deet against A. americanum in the vertical bioassay.

Topics: Animals; DEET; Insect Repellents; Ixodes; Larva; Piperidines; Ticks

The insect repellents N,N-diethyl-3-methylbenzamide (Deet) and the racemate and 1S,2'S stereoisomer of 2-methylpiperidinyl-3-cyclohexene-1-carboxamide (AI3-37220) were tested against Anopheles albimanus Wiedemann and Aedes aegypti (L.) in laboratory human-volunteer assays. Estimated skin doses of Deet or racemic AI3-37220 required to reduce biting by 95% in Ae. aegypti were 2.3 and 3.5 x 10(-2) micromol/cm2 skin, respectively, whereas estimated doses for 95% bite reduction of An. albimanus in an approximately 40-yr-old laboratory colony established from El Salvador were 5 times higher at 12 x 10(-2) micromol Deet/cm2 skin and >20 x 10(-2) micromol/cm2 skin for AI3-37220. In tests with the 1S,2'S stereoisomer of AI3-37220, a newly established colony of An. albimanus from Belize bit less aggressively than El Salvador An. albimanus. However, the Belize-derived mosquitoes were as resistant as the old El Salvador colony to repellent effects of 1S,2'S stereoisomer of 2-methylpiperidinyl-3-cyclohexene-1-carboxamide. Earlier workers surmised that usual skin doses of Deet would offer only limited protection against An. albimanus in the field. Our findings support this speculation, but they also indicate that doses of Deet higher than those needed for protection against Ae. aegypti might offer reasonable protection against An. albimanus. Results indicate that neither racemate nor 1S,2'S stereoisomer of 2-methylpiperidinyl-3-cyclohexene-1-carboxamide offer as much protection as Deet against An. Albimanus, despite being highly effective against Ae. aegypti.

Topics: Aedes; Animals; Animals, Laboratory; Anopheles; DEET; Dose-Response Relationship, Drug; Female; Humans; Insect Bites and Stings; Insecticide Resistance; Male; Piperidines; Species Specificity

The repellent 1-(3-cyclohexen-1-yl-carbonyl)-2-methylpiperidine (AI3-37220) was compared with 2 formulations of diethylmethylbenzamide (deet) for its effectiveness in protecting 4 humans against the bites of Anopheles koliensis mosquitoes at a village in Central Province, Papua New Guinea. A mean of 77.2 +/- 10.5 bites/human/10 min of An. koliensis was collected on ethanol-treated (control) volunteers, a much higher density than most previous studies with Anopheles sp. mosquitoes. The protection provided by all repellents did not last long. Both 25% A13-37220 in ethanol and a formulation containing 35% deet in a gel provided >95% protection for only 2 h. A formulation of 25% deet in ethanol provided only 93% protection 1 h after repellent application and 39% protection 5 h after application.

Topics: Adult; Animals; Anopheles; DEET; Humans; Insect Bites and Stings; Insect Repellents; Male; Papua New Guinea; Piperidines

Racemic 1-[3-cyclohexen-1-ylcarbonyl]-2-methylpiperidine repels blood-feeding arthropods such as mosquitoes, chiggers, and ticks. The compound contains two asymmetric carbon atoms and the racemate consists of four stereoisomers. Quantitative mosquito bioassays using Aedes aegypti (L.) showed that (1S,2'S) and (1R,2'S) configurations were 2.8-3.1 and 1.6-1.8 times more effective, respectively, than the other two stereoisomers in reducing mosquito bites. (1S,2'S) was 2.5 more repellent than the racemate. Biological data show that an interaction of the (2'S)-2-methylpiperidine configuration with a repellent receptor system in A. aegypti is apparently important to repellent activity. Nuclear magnetic resonance spectra and molecular mechanics calculations for the stereoisomers provided insight into the conformation of the (2'S)-group. Results indicate that enhanced repellent effects can be realized through formulation of the most active stereoisomers of the compound.

Topics: Aedes; Animals; Biological Assay; Female; Humans; Insect Repellents; Magnetic Resonance Spectroscopy; Molecular Conformation; Molecular Structure; Piperidines; Stereoisomerism; Structure-Activity Relationship

Acute toxicity and persistence of three insect repellents, deet and two piperidines (AI3-35765 and AI3-37220), were evaluated against mosquito larvae of Aedes albopictus (Skuse) and Anopheles albimanus Wiedemann (Diptera: Culicidae) in the laboratory, and against natural populations of Ae. albopictus in the field. In laboratory studies, the LC50 values of the repellents for first instars ranged between 0.005 and 0.021% (Ae. albopictus) and between 0.01 and 0.014% (An. albimanus) and, for fourth instars, between 0.019 and 0.034% (Ae. albopictus) and between 0.015 and 0.024% (An. albimanus). A 0.1% concentration of deet caused 90-100% mortality in first-instar Ae. albopictus for 4 weeks, whereas AI3-35765 and AI3-37220 at the same concentration killed 95-100% of larvae for 12 weeks and 98-100% of larvae for 33 weeks post-treatment, respectively. Deet and AI3-35765 at 0.1 % concentration resulted in complete mortality of first-instar An. albimanus for 3 weeks post-treatment, whereas AI3-37220 resulted in 91-99% larval mortalities for 35 weeks post-treatment. A 0.1% concentration of A13-37220 provided 77-98% larval mortality for 20 weeks and 63-97% larval mortality for 12 weeks post-treatment, respectively, against fourth-instar Ae. albopictus and An. albimanus. In the field, in artificial containers, the reduction of Ae. albopictus larvae caused by deet, AI3-35765 and AI3-37220 was 88-95% for 3-4 weeks, 98-100% for 7 weeks, and 82-100% for 13 weeks post-treatment, respectively. In used tyres, the same concentration of the repellents resulted in 100% reduction of Ae. albopictus larvae for 2 weeks (deet), 4 weeks (AI3-35765) and 5 weeks (AI3-37220) post-treatment. In cemetery flower vases, Aedes spp. larvae were eliminated for 4 weeks (deet) and 6 weeks post-treatment by both A13-35765 and AI3-37220. These topical repellents (particularly AI3-37220) have good potential for development and use in the management of container-inhabiting mosquitoes because they deter oviposition and kill larvae.

Topics: Aedes; Animals; Anopheles; DEET; Florida; Insect Repellents; Piperidines

A new module for quantitative evaluation of arthropod repellents in human subjects was designed, constructed, and protocols for use of the module were developed. Doses of 3 arthropod repellents, 1-[3-cyclohexen-1-ylcarbonyl] piperidine (AI3-35765), 1-[3-cyclohexen-1-ylcarbonyl]-2-methylpiperidine (AI3-37220), and N,N-diethyl-3-methylbenzamide (deet), were evaluated using the mosquito, Anopheles stephensi Liston. Biting responses to varied doses of the repellents on human skin were quantified, and the effectiveness of the 3 repellents was compared. The new module consists of 6 test cells and permits the simultaneous comparison of up to 5 repellent doses or chemical types and a control using a complete randomized block design with minimal treatment interaction and with > or = 6 replicates per human subject.

Topics: Animals; DEET; Female; Humans; Insect Repellents; Piperidines; Reproducibility of Results

Repellent efficacy of N,N-diethyl-3-methyl-benzamide (deet), the piperidine, 1-[3-cyclohexen-1-ylcarbonyl]-2-methylpiperidine (AI3-37220), and a 1:1 ratio of deet + AI3-37220 were evaluated topically (0.25 mg/cm2 applied in ethanol solution) on human volunteers against the mosquito Aedes communis (DeGeer) and the black fly Simulium venustum Say. The average repellency of all three formulations was > 95% at 4 h. For both mosquitoes and black flies, deet alone provided < 90% protection at 6 h, whereas AI3-37220 provided > 95% protection. Although repellent treatments were not significantly different overall, the contrasts between AI3-3720 versus deet were significant at 6 and 8 h. The 95% confidence interval on percent repellency at 6 h ranged from 90.1 to 98.9% for AI3-37220 versus 64.3 to 82.2% for deet, and at 8 h ranged 76.1 to 88.5% for AI3-37220 versus 47.8 to 64.0% for deet. Similarly, the confidence interval for protection against black flies at 6 h by (AI3-37220 ranged from 86.3 to 99.5% and did not overlap with the confidence interval provided by deet alone (51.2 to 78.8%). There was no evidence of synergistic repellency from a combination of the two compounds; i.e., protection from combined compounds was no better than either repellent used alone.

Topics: Aedes; Animals; DEET; Female; Humans; Insect Control; Insect Repellents; Mosquito Control; New York; Piperidines; Simuliidae

N,N-diethyl-3-methylbenzamide (DEET) has recently been reported to kill cercariae of Schistosoma mansoni in vitro. In addition, it blocked cercarial entry into mouse tail skin. We confirmed these results and compared the efficacy of DEET to a second insect repellent, 1-(3-Cyclohexen-1-yl-carbonyl)-2-methylpiperidine (AI3-37220), in preventing S. mansoni infections in mice. Both AI3-37220 and DEET conferred 100% protection against S. mansoni infection via percutaneous exposure to cercariae.

Topics: Animals; DEET; Insect Repellents; Intestines; Liver; Male; Mice; Mice, Inbred CBA; Piperidines; Schistosoma mansoni; Schistosomiasis mansoni; Skin

Four repellents, N,N-diethyl-3-methyl-benzamide (deet), 2-hydroxy-methyl-cyclohexyl acetic acid lactone (CIC-4), and 2 piperidines (1-[3-cyclohexen-1-ylcarbonyl] piperidine [AI3-35765] and 1-[3-cyclohexen-1-ylcarbonyl]-2-methylpiperidine [AI3-37220]) were evaluated alone and in combination against Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus using a modified in vitro test system. This method was a valuable tool for comparing effective concentrations of the new compounds. Because of the controlled conditions of the test, it was possible to use the results of assays that had been conducted over a 5-year period and to perform the many replications necessary to evaluate combinations of compounds. The new candidate repellents were generally as effective as deet. Although speculative at this time, there was some evidence of synergistic interaction. Repellent combinations of CIC-4/AI3-37220/AI3-35767, deet/AI3-35765, and deet/AI3-37220/AI3-35765 against An. stephensi and CIC-4/AI3-35765, deet/AI3-37220/AI3-35765, AI3-37220/AI3-35765, and CIC-4/AI3-37220 against Ae. aegypti were more effective than the component compounds alone.

Topics: Aedes; Animals; Anopheles; Chromones; Culex; DEET; Evaluation Studies as Topic; Female; Insect Repellents; Mosquito Control; Piperidines

The repellents diethylmethylbenzamide (deet), (2-hydroxymethylcyclohexyl) acetic acid lactone (CIC-4), and 1-(3-cyclohexen-1-yl-carbonyl)-2-methylpiperidine (AI3-37220) were compared for their effectiveness in protecting 5 soldiers against the bites of Anopheles spp. at a village in Papua New Guinea. All 3 repellents, applied as 25% ethanol concentrations, provided > or = 95% protection against primarily An. farauti 4 for at least 3 h after application.

Topics: Animals; Anopheles; Chromones; DEET; Evaluation Studies as Topic; Humans; Insect Repellents; Mosquito Control; Papua New Guinea; Piperidines

Laboratory and field tests of the repellents diethyl methylbenzamide (deet), 1-(3-cyclohexen-1-yl-carbonyl)-2-methylpiperidine (AI3-37220), and (2-hydroxymethylcyclohexyl) acetic acid lactone (CIC-4) were conducted against Anopheles farauti s.s. Laveran, an important malaria vector in the southwest Pacific region. In the laboratory, An. farauti was tolerant of all 3 repellents, but deet and CIC-4 provided significantly better protection than AI3-37220. The field study was conducted in rain forest located near Innisfail, northern Queensland, and tested 25% (vol:vol) ethanol solutions of each repellent against An. farauti. All 3 repellents provided > 95% protection against An. farauti for 5 h after application. In contrast to the laboratory tests, protection provided by AI3-37220 was significantly better than that by either deet or CIC-4, and there was no difference between protection by deet and CIC-4. The protection by deet and CIC-4 declined 8 h after application and provided < or = 50% protection at 9 h. In contrast, AI3-37220 provided > or = 94% protection for 9 h.

Topics: Animals; Animals, Laboratory; Animals, Wild; Anopheles; Australia; Chromones; DEET; Female; Forearm; Humans; Insect Repellents; Male; Piperidines; Skin

Laboratory and field tests of the repellents diethyl methylbenzamide (deet), 1-(3-Cyclohexen-1-yl-carbonyl)-2-methylpiperidine (AI3-37220), and (2-hydroxymethylcyclohexyl) acetic acid lactone (CIC-4) were conducted against Anopheles dirus Peyton & Harrison, the principal malaria vector in Thailand. In the laboratory, An. dirus was more sensitive to CIC-4 than either AI3-37220 or deet. The duration of protection provided by each repellent in laboratory tests increased with higher concentrations of repellents and when exposed in cages containing fewer mosquitoes. A field study in Chanthaburi Province, southeastern Thailand, during November 1993 tested 25% (wt:wt) ethanol solutions of each repellent against An. dirus. In contrast to the laboratory experiments, protection provided by AI3-37220 was significantly better than either deet or CIC-4 and there was no significant difference between deet and CIC-4. Protection provided by deet and CIC-4 fell to below 95% 2 h after repellent application, whereas AI3-37220 provided > 95% protection for 4 h. The protection provided by all repellents fell to < or = 65% 7 h after repellent application.

Topics: Aedes; Animals; Anopheles; Chromones; DEET; Female; Humans; Insect Repellents; Mosquito Control; Piperidines; Thailand

A field evaluation of the repellents N,N-diethyl-3-methylbenzamide (deet) and 1-(3-cyclohexen-1-yl-carbonyl)-2-methylpiperidine (AI3-37220, a piperidine compound) was conducted against Anopheles funestus and An. arabiensis in Kenya. Both repellents provided significantly more protection (P < 0.001) than the ethanol control. AI3-37220 was significantly more effective (P < 0.001) than deet in repelling both species of mosquitoes. After 9 h, 0.1 mg/cm2 of AI3-37220 provided 89.8% and 71.1% protection against An. arabiensis and An. funestus, respectively. Deet provided > 80% protection for only 3 h, and protection rapidly decreased after this time to 60.2% and 35.1% for An. arabiensis and An. funestus, respectively, after 9 h. Anopheles funestus was significantly less sensitive (P < 0.001) to both repellents than An. arabiensis. The results of this study indicate that AI3-37220 is more effective than deet in repelling anopheline mosquitoes in western Kenya.

Topics: Adult; Animals; Anopheles; DEET; Humans; Insect Repellents; Kenya; Male; Mosquito Control; Piperidines

Four repellents, deet, AI3-37220, AI3-35765, and CIC-4, prepared as 12.5% ethanol solutions, were evaluated against biting midges on Stansbury Islands, UT. Leptoconops americanus Carter was the only species that was biting human volunteers during the study. This species bit primarily on the ears at rates up to 840 bites per hour. All four repellents significantly reduced the number of bites on treated volunteers. AI3-37220 consistently provided the longest period of protection, giving 97 and 74% protection at 4 and 8 h, respectively. In a direct statistical comparison, AI3-37220 significantly outperformed deet. CIC-4 and AI3-35765 were the least effective repellents, providing 45-47% protection 8 h after application.

Topics: Animals; Ceratopogonidae; Chromones; DEET; Insect Control; Insect Repellents; Piperidines; Utah

Repellent efficacy of deet (N,N-diethyl-3-methylbenzamide) and a piperidine, AI3-37220, was evaluated topically on human volunteers against lone star tick, Amblyomma americanum (L.), nymphs and adults in the field. AI3-37220, at 0.5 mg/cm2, provided > 90% repellency against adult and nymphal ticks over a 6-h test period and showed significantly better repellent efficacy than deet. Deet, at the same concentration, provided 85% repellency at 0 h and deteriorated to 55% repellency at 6 h.

Topics: Animals; DEET; Evaluation Studies as Topic; Female; Humans; Insect Repellents; Male; Piperidines; Tick Control; Ticks

A field experiment was conducted to compare the biting behavior of Plasmodium falciparum-infected and uninfected Anopheles on humans using mosquito repellents. Repellent formulations (5% [wt/vol] N,N-diethyl-3-methylbenzamide [deet] or 5% [wt/vol] AI3-37220, a piperidine compound, both in 100% ethanol, or 100% ethanol alone [as a control]) were applied to the lower legs of 3 collectors in each of 4 houses. Collectors caught mosquitoes over 6 collection nights. Mosquitoes were collected into vials after they initiated probing on the leg of a collector. Infected females made up the same proportion of the Anopheles funestus populations biting either repellent-protected or unprotected individuals. We conclude that repellent formulations are equally effective against Plasmodium-infected and uninfected An. funestus.

Topics: Animals; Anopheles; DEET; Feeding Behavior; Female; Host-Parasite Interactions; Humans; Insect Repellents; Insect Vectors; Malaria; Piperidines; Plasmodium falciparum

Deet (N,N-diethyl-3-methyl-benzamide), the lactone CIC-4 ([2-hydroxy-methyl-cyclohexyl] acetic acid lactone), the USDA Proprietary Chemicals AI3-37220 (1- [3-cyclohexen-1-ylcarbonyl]-2-methylpiperidine) and ++[3-35765 (1-[3-cyclohexen-1-ylcarbonyl] piperidine), and the U.S. military extended duration repellent formulation (EDRF) of deet were evaluated for repellency in the laboratory and field against the black flies Prosimulium mixtum and P. fuscum. CIC-4, AI3-37220, and AI3-35765 were as effective as deet at repelling P. mixtum and P. fuscum in laboratory and field experiments. Only the EDRF provided significantly longer protection than the deet standard against these black flies in the field.

Topics: Animals; Chromones; DEET; Female; Humans; Insect Bites and Stings; Insect Repellents; Piperidines; Simuliidae